bims-fagtap 2025-12-07 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–12–07
38 papers selected by
Luca Bolliger, lxBio

AI-Driven Structural Elucidation of the Bacteriophage KP32: Decoding Its Molecular Arsenal Against Klebsiella Pneumoniae.
Neutrophils, not macrophages, aid phage-mediated control of pulmonary Pseudomonas aeruginosa infection.
Synergy between ciprofloxacin and temperate phages overcomes therapeutic limitations caused by lysogen formation.
Characterisation of four novel bacteriophages targeting carbapenem-resistant Klebsiella pneumoniae and their lytic activity alone and in combination.
Prolonged disease remission of the chronic immunological skin disorder hidradenitis suppurativa with adjunctive bacteriophage therapy.
Considerations and perspectives on phage therapy from the transatlantic taskforce on antimicrobial resistance.
Phages and quorum sensing: findings to consider in phage therapy.
Phage Therapy for Hospital-Acquired Respiratory Bacterial Infections: A Review.
Advancements in alternative approaches to address antimicrobial resistance in bacterial pneumonia: a comprehensive review.
Integrated Evaluation of IL-8 Levels and the In Silico and In Vitro Effects of Ellagic Acid against Extended-spectrum β-lactamase in Biofilm-forming Klebsiella pneumoniae Isolated from Urinary Tract Infections.
Beyond Antibiotics: Emerging Therapies for Pseudomonas aeruginosa in Diabetic Foot Infections.
Evolving strategies of intracellular Hypervirulent Klebsiella pneumoniae during phage therapy: Reducing host autophagy and inflammation.
The use of Pretiva™ negative pressure therapy provides benefits in the management of hard-to-heal chronic wounds: A case series.
Nanobiotics to tackle efflux-mediated resistance in bacterial pathogens.
In silico approaches for discovering microbial antiviral defense systems.
Biofilm in Diabetic Foot Ulcers: A Systematic Narrative Review.
Combined application of novel broad-spectrum bacteriophages and antagonistic bacterial strain: enhanced biocontrol efficacy against Streptomyces induced potato common scab.
Defect-complementation homologous recombination: A novel strategy for precise genome engineering of virulent phages.
Immunological pathways triggered by Porphyromonas gingivalis in periodontitis: New insights into molecular mechanisms.
Eying up predatory bacteria: living antimicrobials for ocular infections.
Dysbiosis and Therapeutic Modulation of the Gut Microbiota in Multiple Sclerosis: A Narrative Review.
Self-Adaptive Wound Dressings for Wound Healing and Repair.
Virtual Wound Care in Australian Nursing Homes: Protocol for a Pilot and Feasibility Study.
The oral microbiome in aging: a window into health and longevity.
Characterization of bacteriophages infecting Escherichia coli associated with bovine mastitis.
Cell and Gene Therapy: Transforming Treatment Paradigms for Patient-Centric Care.
Artificial intelligence for surgical data management and decision support: lessons from wound care.
Deconstructing gene therapy in hemophilia for the clinician.
Opportunities and challenges in applying microbiota to clinical cancer immunotherapy.
Microbiology of Pressure Ulcers: A Systematic Review.
MetaMDA: explainable prediction of microbe-drug association utilizing random walks on a microbe-metabolite-drug heterogeneous network.
Recombinant Molecules as a New Frontier in Mucositis Therapy.
Harnessing the Microbiome in Cancer Immunotherapy: Regulation, Prediction, and Therapeutic Targeting.
Incisional Negative Pressure Wound Therapy After Inguinal Vascular Surgery Reduction SSI and Mortality: A Systematic Review and Meta-analysis.
Quantitative Imaging for Interstitial Lung Disease.
The effect of autologous platelet-rich plasma on donor site wound healing: a randomised crossover clinical trial.
Failure of Empirical Antimicrobial Therapy in Diabetic Foot Ulcer With Chronic Osteomyelitis: A Case Report.
Theranostics Education and Training.

Front Biosci (Landmark Ed). 2025 Nov 26. 30(11): 46489

AI-Driven Structural Elucidation of the Bacteriophage KP32: Decoding Its Molecular Arsenal Against Klebsiella Pneumoniae.

Mario Privitera, Giovanni Barra, Flavia Squeglia, Zuzanna Drulis-Kawa, Valeria Napolitano, Rita Berisio.

   BACKGROUND: Klebsiella pneumoniae is one of the most critical Gram-negative bacteria according to the World Health Organization (WHO). Due to the ability of this bacterium to evade antibiotics, phage therapy is becoming a promising tool. However, the use of isolated proteins rather than entire phages could reduce several risks associated with phage replication. Thus, understanding the protein composition and structural organization of bacteriophages is crucial for unlocking their biology and holds great potential for medicine and biotechnology.
METHODS: In this study, artificial intelligence with AlphaFold 3.0 (AF3) and bioinformatic analysis were used to model the hitherto unknown structure of the Klebsiella phage KP32 (KP32), a complex and selective phage that targets K. pneumoniae strains with the K3 and K21/KL163 capsular serotypes.
RESULTS: By combining AF3 with sequence and structure analysis, we reconstructed the entire phage KP32. This complex phage is composed of over 500 protein chains, of which 415 compose its capsid and 104 its core-portal-tail complex, a platform that allows the phage to adhere to K. pneumoniae, hydrolyze its capsular sugars and finally inject its genetic code into the bacterium.
CONCLUSIONS: Phage therapy is a potentially promising tool for controlling antimicrobial resistance (AMR). However, one limitation arises from the limited knowledge of their nature and mechanisms of action, as only a few phages have been structurally characterized. The reconstruction of entire phages is currently a viable strategy for elucidating their mechanistic properties, knowledge that will enhance their potential applications as therapeutic alternatives.

Keywords:  Klebsiella pneumoniae; artificial intelligence; bacteriophage; protein structure

DOI:  https://doi.org/10.31083/FBL46489
Front Immunol. 2025 ;16 1681461

Neutrophils, not macrophages, aid phage-mediated control of pulmonary Pseudomonas aeruginosa infection.

Chantal Weissfuss, Karen Hoffmann, Ulrike Behrendt, Magdalena Bürkle, Shailey G Twamley, Imke H E Korf, Katharina Ahrens, Christine Rohde, Christian M Zobel, Laurent Debarbieux, Jean-Damien Ricard, Martin Witzenrath, Geraldine Nouailles.

   Background: The increasing prevalence of multidrug-resistant (MDR) bacteria has reduced the effectiveness of standard antibiotics, prompting renewed interest in bacteriophage (phage) therapy as an alternative or adjunctive treatment. Phage therapy offers high specificity, self-amplification at infection sites, and minimal disruption to the gut microbiota. However, clinical implementation is challenging, due to the risk of phage resistance and uncertainties regarding optimal dosing and immune interactions.
Methods: Previously, we demonstrated that a two-phage cocktail exhibited low immunogenicity in mice and, when combined with meropenem, significantly improved clearance of ventilator-associated Pseudomonas aeruginosa pneumonia, reduced inflammation, and disrupted biofilms more effectively than either treatment alone. In the present study, we investigated the interplay between this phage cocktail and innate immune defenses using a murine respiratory infection model and human in vitro assays.
Results: Our findings reveal that the therapeutic efficacy of phage treatment is critically dependent on the presence of neutrophils, which act synergistically with phages to achieve effective bacterial clearance, particularly when bacterial burden exceeds a defined threshold. Alveolar macrophages, however, do not significantly contribute to infection resolution in vivo.
Conclusion: Since neutrophils play a key-role in supporting phage-mediated Pseudomonas clearance, the efficacy of phage therapy is closely linked to the hosts immune competence - an important consideration when treating immunocompromised patients.

Keywords:  Pseudomonas aeruginosa; immunophage synergy; innate immunity; phage therapy; pneumonia

DOI:  https://doi.org/10.3389/fimmu.2025.1681461
Sci Rep. 2025 Dec 05.

Synergy between ciprofloxacin and temperate phages overcomes therapeutic limitations caused by lysogen formation.

P Lauman, T R H Cassell, J J Dennis.

  Bacteriophages have proven invaluable in combatting drug-resistant bacteria. Bias towards exclusive use of obligately lytic phages has restricted the range of phage therapy, however, since at least half of all Caudovirecetes are temperate, and such phages remain the only option available for many problematic pathogens - including the notorious members of the Burkholderia cepacia complex (Bcc). Temperate phage-antibiotic synergy (tPAS), a unique strategy that leverages lysogen-forming phages as adjuvants to traditional antibiotics, has been validated for phages infecting E. coli and P. aeruginosa and is a major step towards normalization of temperate phages in therapeutics. In this report, we extend tPAS to Burkholderia phages and show that combining these phages with subinhibitory doses of ciprofloxacin overcomes natural limitations in antibacterial activity caused by lysogen formation. We further demonstrate that the magnitude of this effect correlates with the lysogenization frequencies of utilized phages, meaning tPAS is tailored specifically to otherwise ineffective, highly lysogenic phages. Finally, we observed heterogeneity in lysogen depletion rates among synergizing phages, suggesting 'complete' lysogen depletion is not required for antibacterial synergy. Our results support the use of temperate phages as synergizing adjuvants against Bcc species, thereby substantially expanding the limited arsenal of tools available for combating these pathogens.

Keywords:   Burkholderia cepacia complex; Bacteriophage; Lysogen depletion; Lysogenization frequency; Phage therapy; Temperate phages; tPAS

DOI:  https://doi.org/10.1038/s41598-025-30556-7
Curr Res Microb Sci. 2025 ;9 100509

Characterisation of four novel bacteriophages targeting carbapenem-resistant Klebsiella pneumoniae and their lytic activity alone and in combination.

Elisa Fausti, Andrea Bonacorsi, Novella Cesta, Cesira Giordano, Simona Barnini, Magda Marchetti, Claudia Campobasso, Rob Lavigne, Anna Altieri, Cartesio D'Agostini, Marco Iannetta, Vincenzo Malagnino, Arianna Tavanti, Loredana Sarmati, Mariagrazia Di Luca.

  Klebsiella pneumoniae is a nosocomial pathogen with rising levels of antibiotic resistance, increasing interest in bacteriophage therapy as an adjunct or alternative treatment. This study aimed to isolate and characterise bacteriophages active against multidrug-resistant K. pneumoniae and evaluate their efficacy. Four lytic phages, Kilian, Trimon, Jurek, and Olmo were isolated from water sources using K. pneumoniae ATCC BAA-2146 as host. Genome analysis revealed no known lysogeny, antibiotic resistance, or virulence-associated genes, supporting their suitability for therapeutic use. Electron microscopy classified Kilian, Trimon, and Jurek as siphoviruses, and Olmo as a myovirus. All phages showed rapid adsorption (2.5-5 min), short latent periods (5-15 min), and variable burst sizes (22-474 PFU/cell). The phages exhibited a narrow host range, collectively infecting 13 out of 90 tested K. pneumoniae clinical isolates, including carbapenemase producers and high-risk clones (ST11, ST512, ST147, ST307, ST37). The phages were then formulated into a cocktail and tested in vitro, showing enhanced and sustained bacterial growth suppression compared to single phages, with strain- and multiplicity of infection-dependent effects. Antibiofilm activity was assessed on preformed biofilms grown on porous glass beads. Three hours after treatment, both individual phages and the cocktail reduced viable biofilm-associated cells >4-log10 compared to untreated controls. Finally, high titers of purified phages obtained by cesium chloride gradient ultracentrifugation showed no adverse effects on Galleria mellonella viability, indicating a safe profile. These findings support the potential of phage combinations to target multidrug-resistant and biofilm-associated K. pneumoniae infections.

Keywords:  Antibiofilm activity; Antibiotic resistance; Bacteriophage; Carbapenem resistance; Klebsiella pneumoniae; Phage cocktail; Phage therapy

DOI:  https://doi.org/10.1016/j.crmicr.2025.100509
Nat Commun. 2025 Dec 02.

Prolonged disease remission of the chronic immunological skin disorder hidradenitis suppurativa with adjunctive bacteriophage therapy.

Lene Bens, Tine Vanhoutvin, Sabrina Green, Sayali Gorivale, Madalena Almeida, Filip Romaniuk, Tom Hillary, Daan Jansen, Jelle Matthijnssens, Séverine Vermeire, João Sabino, Melissa Depypere, David Devolder, Isabel Spriet, Yves Debaveye, Paul De Munter, Jolien Onsea, Willem-Jan Metsemakers, Vera van Noort, Jean-Paul Pirnay, Maya Merabishvili, Jeroen Wagemans, Rob Lavigne, An Van Laethem.

Hidradenitis suppurativa (HS) is a chronic skin disease in which the acute development of noduli, abscesses and in a later stage fistulas remains difficult to control, despite a wide range of recommended treatment options including immunomodulatory biologicals, surgical intervention and antibiotics. Besides being painful, associated lesions have an extensive impact on the quality of life. While HS is primarily an immune-mediated inflammatory disease, the skin microbiota plays a key role in its pathogenesis with pathogenic bacterial colonization of lesions observed. Bacteriophages, the viruses of bacteria, are used to treat a 52-year-old female HS patient with re-current colonization of lesions with Staphylococcus aureus. Phage therapy results in complete removal of lesions with a flare-free period of six months, along with a substantial improvement in the patient's quality of life. The deployed experimental framework and the gained clinical experience will be valuable for future HS phage therapy research.

DOI: https://doi.org/10.1038/s41467-025-65939-x
Nat Commun. 2025 Dec 04. 16(1): 10883

Considerations and perspectives on phage therapy from the transatlantic taskforce on antimicrobial resistance.

Kyung Moon, Carmen Coxon, Christine Årdal, Radu Botgros, Sarah Djebara, Laura Durno, Cara R Fiore, Jean-Baptiste Perrin, Dennis M Dixon, Marco Cavaleri.

Amid rising antimicrobial resistance and limited antibiotic innovation, bacteriophages are gaining attention as potential therapeutics across human health, animal, and food sectors. Despite historical use, their clinical application in humans remains constrained by scientific, industrial, and regulatory challenges. To address these issues, the Transatlantic Task Force on Antimicrobial Resistance (TATFAR) convened sessions with experts from member parties. This perspective synthesizes insights from the TATFAR group, highlighting regulatory differences, research gaps, and opportunities for international collaborations to advance bacteriophage therapy.

DOI: https://doi.org/10.1038/s41467-025-64608-3
Eur J Clin Microbiol Infect Dis. 2025 Dec 03.

Phages and quorum sensing: findings to consider in phage therapy.

Laura Fernández-Garcia, Lucia Blasco, Inés Bleriot, Lucía Arman, Clara Ibarguren-Quiles, Antonio Barrio-Pujante, Manuel González de Aledo, Rodolfo García-Contreras, Rafael Cantón, Thomas K Wood, María Tomas.

   PURPOSE: This review aims to provide an overview of current knowledge on the involvement of QS in phage infection. The role of QS in bacterial defence against phages is emphasized, without overlooking the fact that QS can sometimes also promote phage infection. We also review the implications of QS in phage therapy and current perspectives.
METHODS: For the bibliographic review, PubMed and Google Scholar were used to search for publications on "quorum-sensing" and "phage infection".
RESULTS: The relationships between bacteria and phages are extremely complicated and involve several mechanisms. Quorum sensing (QS) is a communication system involved in controlling bacterial fitness, both at population and individual levels. Phages (viruses that infect bacteria) play a major role in the natural regulation of bacterial populations. In order to protect themselves, bacteria have developed several defence mechanisms involving different levels of protection, such as prevention of phage entry and phage assembly, degradation of phage nucleic acids, and entrance in a dormant state (persistence). QS has recently been shown to affect some of these phage defence mechanisms. In this review, the main influence of QS in phage infection is discussed. Finally, some innovative treatment approaches, including using engineered phages harbouring T7aiiA QQ enzyme and QS inhibitors such as SsoPox-W2631 and penicillinic acid, are also considered. However, it is important to note that the use of QS-interfering molecules may also reduce the efficacy of phage therapy.
CONCLUSION: QS is an important mechanism that affects several bacterial metabolisms, particularly in phage defence. Despite the complex interaction between QS and phages, modifying QS has been found to enhance phage therapy.

Keywords:  Bacterial defence; Phage infection; Phage therapy; Quorum sensing

DOI:  https://doi.org/10.1007/s10096-025-05375-3
Open Respir Arch. 2026 Jan-Mar;8(1):8(1): 100507

Phage Therapy for Hospital-Acquired Respiratory Bacterial Infections: A Review.

Maria-Carmen Muñoz-Egea, Alianet Rodríguez, Jaime Esteban, Meritxell García-Quintanilla.

  Antibiotic-resistant respiratory infections necessitate alternative or adjunctive therapeutic strategies to reduce the bacterial burden in patients, particularly in the context of hospital-acquired infections. Bacteriophage therapy has emerged as a promising tool, with a resurgence of research in Western countries for various infectious diseases. The application of phage therapy against pulmonary infections has been primarily investigated for pathogens such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii in in vivo experiments and for Mycobacterium abscessus and P. aeruginosa in compassionate use cases. This review summarizes recent work on phage therapy targeting clinically relevant drug-resistant bacteria that cause nosocomial pulmonary infections, encompassing animal research, clinical cases, and clinical trials.

Keywords:  Antimicrobial resistance; Hospital-acquired pneumonia; Multidrug resistance; Phage therapy; Respiratory infections

DOI:  https://doi.org/10.1016/j.opresp.2025.100507
Front Microbiol. 2025 ;16 1704931

Advancements in alternative approaches to address antimicrobial resistance in bacterial pneumonia: a comprehensive review.

Dala N Daraghmeh, Roaa Waleed AbuIriban, Nour Nawawreh, Ansam Mahmoud Abuamro, Momin M Alassar, Salahaldeen N Daraghma, Nesma M Alhajahmed, Yasmeen Thandar.

   Purpose: This review explores both current and emerging alternative treatment approaches to combat AMR specifically in the context of bacterial pneumonia, highlighting therapies that extend beyond conventional antibiotics.
Methods: PubMed, Embase, and Google Scholar were searched for full-text, English-language articles, with emphasis on publications from 2020 to 2025. Earlier seminal studies were also included when necessary to provide historical, mechanistic, or conceptual context. The review focuses was on alternative strategies that have shown effectiveness in preclinical or clinical settings to combat AMR in relation to bacterial pneumonia.
Results: Emerging strategies to tackle AMR in bacterial pneumonia involve several innovative approaches including stem cells, bacteriophage therapy, metal based nanoparticles (e.g., silver, copper, and gold). The adjunctive use of probiotics and herbal medicine has demonstrated potential in enhancing clinical outcomes and modulating host immunity. Moreover, gene editing technologies like CRISPR-CAS and various vaccination programs are being investigated for their roles in prevention and resistance management. While these methods show promise, many are still in the early stages of development and encounter challenges related to standardization, safety, and regulatory approval.
Conclusion: Alternative therapies present exciting possibilities for addressing AMR in bacterial pneumonia. However, to effectively translate these innovations into clinical practice, we need thorough research, international collaboration, and supportive policy frameworks. By combining these strategies with antimicrobial stewardship initiatives, we can help maintain antibiotic effectiveness and enhance patient outcomes.

Keywords:  AMR; MDR; bacterial pneumonia; phage; probiotics; stem cells

DOI:  https://doi.org/10.3389/fmicb.2025.1704931
Rev Recent Clin Trials. 2025 Nov 29.

Integrated Evaluation of IL-8 Levels and the In Silico and In Vitro Effects of Ellagic Acid against Extended-spectrum β-lactamase in Biofilm-forming Klebsiella pneumoniae Isolated from Urinary Tract Infections.

Mohammed Mukhles Ahmed, Haneen Emad Khadum, Samer N Khalaf, Ali Hazim Abdulkareem.

   INTRODUCTION: Urinary tract infections (UTIs) caused by multidrug-resistant, biofilmforming Klebsiella pneumoniae represent a serious global health concern. Conventional antibiotics often fail due to resistance and biofilm-associated tolerance, necessitating novel diagnostic and therapeutic strategies. This study investigated interleukin-8 (IL-8) as a diagnostic marker and evaluated the anti-virulence potential of ellagic acid against extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae.
METHODS: This study was a cross-sectional, experimental, and analytical investigation conducted from August 2023 to March 2024. Serum IL-8 levels were quantified in patients and healthy controls using ELISA. The antibiotic susceptibility of K. pneumoniae isolates was assessed according to CLSI guidelines, and ESBL activity was determined by the nitrocefin hydrolysis test. Biofilm formation was quantified using the crystal violet assay, with and without ellagic acid treatment. In silico docking studies were conducted using AutoDock Vina to predict interactions between ellagic acid and the CTX-M-15 β-lactamase, Wza, FabH, and SdiA proteins.
RESULTS: IL-8 levels were significantly higher in patients (223.8 ± 43.5 pg/mL) compared with controls (47.9 ± 17.3 pg/mL; p < 0.0001). All isolates were resistant to ampicillin and showed broad resistance to other antibiotics. Ellagic acid significantly reduced biofilm biomass (p = 0.0002) but concurrently increased ESBL activity (p = 0.0001). Docking demonstrated that ellagic acid was strongly bound to CTX-M-15 (-8.3 kcal/mol), had moderate interactions with Wza and SdiA, whereas the interaction with FabH was relatively low.
DISCUSSION: The high concentration of IL-8 supports its use as a biomarker to detect K. pneumoniae infections. The elevated resistance profile of K. pneumoniae to antibiotics highlights the urgent need for alternative treatment approaches. Though ellagic acid increased ESBL activity, it showed distinct antibiofilm activity and responses with virulence-related proteins, indicating a modulatory action that may reduce bacterial pathogenicity. Limitations include the lack of in vivo validation and the need to mechanistically elucidate the modulation of ESBL.
CONCLUSION: IL-8 is a valuable biomarker for ESBL-producing K. pneumoniae infection. Ellagic acid reduces biofilm formation and targets bacterial resistance and virulence proteins, supporting its potential as a natural anti-virulence agent against multidrug-resistant K. pneumoniae.

Keywords:  ESBLs; Ellagic acid; IL-8; Klebsiella pneumoniae; UTI; biofilm; molecular docking.

DOI:  https://doi.org/10.2174/0115748871349421251105115035
Int J Low Extrem Wounds. 2025 Dec 03. 15347346251403644

Beyond Antibiotics: Emerging Therapies for Pseudomonas aeruginosa in Diabetic Foot Infections.

Irene Terzi, Dimitrios Dimitriadis, Melina Ntoga.

  Diabetic foot infections (DFIs) caused by Pseudomonas aeruginosa are notoriously difficult to treat due to multidrug resistance, biofilm formation, and impaired tissue perfusion. This narrative review summarises emerging non-antibiotic and adjunctive therapies beyond conventional antimicrobial regimens. We highlight the potential of bacteriophage therapy, antimicrobial peptides, quorum sensing inhibitors, biofilm-disrupting enzymes, nanotechnology-based delivery systems, monoclonal antibodies, iron metabolism inhibitors, and photodynamic therapy. Each of these offers unique mechanisms to disrupt biofilms, neutralise virulence, or enhance immune clearance. In addition, we review advanced localized delivery platforms and diagnostic-guided personalized regimens optimizing intra-wound efficacy. Most of these novel interventions remain investigational, based on preclinical models, early-phase trials, or case reports. Nevertheless, they appear promising in managing chronic, refractory P. aeruginosa DFIs. Integration of these strategies into clinical practice will depend on robust clinical trials, regulatory clarity, and precision diagnostics. By moving beyond antibiotics, this evolving therapeutic landscape offers hope for improved outcomes in a population at high risk for limb loss and systemic complications.

Keywords:  Pseudomonas aeruginosa; bacteriophage therapy; biofilm disruption; diabetic foot infections; non-antibiotic therapies

DOI:  https://doi.org/10.1177/15347346251403644
Virulence. 2025 Dec 04. 2600148

Evolving strategies of intracellular Hypervirulent Klebsiella pneumoniae during phage therapy: Reducing host autophagy and inflammation.

Huale Chen, Yao Sun, Zeyu Huang, Deyi Zhao, Jingchun Kong, Huanchang Chen, Cui Zhou, Tieli Zhou.

  Hypervirulent Klebsiella pneumoniae (hvKp) presents challenges in infection management due to antibiotic resistance associated with its intracellular persistence. This study investigates the efficacy of phage therapy against intracellular hvKp using a two-stage murine model. We assessed changes in virulence, host survival, and immune responses through phagocytosis assays, transmission electron microscopy, and Western blotting, complemented by transcriptomic and proteomic analyses. Results indicate that phage therapy reduces mortality and modulates bacterial virulence by downregulating capsule production. Following phage exposure, hvKp adapts by enhancing its oxidative stress resistance. Crucially, these adaptations weaken host inflammatory and autophagy responses, enabling better survival within host cells. These adaptations suggest that while phage therapy can mitigate infection severity, the capacity of hvKp to modulate host pathways underscores the complexity of treating intracellular infections and highlights the importance of targeting both bacterial and cellular responses.

Keywords:  Hypervirulent klebsiella pneumoniae; autophagy; immune modulation; intracellular survival; phage therapy

DOI:  https://doi.org/10.1080/21505594.2025.2600148
Int J Surg Case Rep. 2025 Nov;pii: S2210-2612(25)01169-1. [Epub ahead of print]136 111983

The use of Pretiva™ negative pressure therapy provides benefits in the management of hard-to-heal chronic wounds: A case series.

Wolmark Xiques-Molina, Katrwin Pérez-Camacho, Ana Vidal-Bastidas, Ariel González-Arnedo, Johana Galván-Barrios, Patricia Delgado.

   INTRODUCTION AND IMPORTANCE: Chronic wounds pose a major global health challenge, often leading to prolonged disability, increased healthcare costs, and significant patient suffering. Conventional therapies frequently fail to achieve complete healing in complex cases, highlighting the need for innovative, cost-effective solutions. Portable negative pressure wound therapy devices (NPWT), offer new opportunities to enhance wound healing, particularly in emerging healthcare systems.
CASE PRESENTATION: We report two cases of patients with hard-to-heal lower limb wounds. The first case involved a 48-year-old male with a chronic venous ulcer and repeated soft tissue infections. The second case involved a 52-year-old female with a chronic post-traumatic wound unresponsive to multiple surgical interventions. Both patients demonstrated significant clinical improvement following the application of Pretiva™ NPWT, including tissue regeneration, reduction of wound area, absence of exudate and odor, and decreased risk of limb loss.
CLINICAL DISCUSSION: These cases illustrate how NPWT effectively reactivated healing in wounds that had stagnated under conventional care. The therapy's mechanisms enhancing microcirculation, reducing edema, and promoting granulation tissue formation, translated into rapid, clinically meaningful outcomes. The portability and ease of use of NPWT also support its feasibility in outpatient and resource-limited settings, addressing key gaps in chronic wound management in emerging countries.
CONCLUSION: This case series illustrates the potential therapeutic value of Pretiva™ NPWT in the management of hard-to-heal chronic wounds. Its observed effectiveness and practical feasibility in outpatient and resource-constrained settings suggest it may be a valuable option in similar clinical contexts.

Keywords:  Negative-pressure wound therapy; Surgical wound; Wound closure techniques; Wounds and Injuries

DOI:  https://doi.org/10.1016/j.ijscr.2025.111983
Crit Rev Microbiol. 2025 Dec 03. 1-23

Nanobiotics to tackle efflux-mediated resistance in bacterial pathogens.

Barani Devi Thillai, Sudarshan Kini, Vijaya Kumar Deekshit.

  Efflux-mediated resistance is a critical mechanism by which bacterial pathogens evade antibiotic treatment, posing significant challenges to effective infection management. As the first line of defence mechanism in bacteria, efflux pumps actively expel antibiotics, contributing to multidrug resistance. Recent advances in nanotechnology offer promising solutions, with nanobiotics emerging as a novel approach to combating efflux-mediated resistance. Nanobiotics are engineered nanoscale materials with antibacterial properties. They can be designed to inhibit efflux pump function, enhance drug accumulation, and disrupt bacterial cell membranes, thereby overcoming traditional resistance mechanisms. Nanobiotics can easily fuze with the bacterial cell wall and facilitate the release of antibiotics into the cytoplasm. This review provides an overview of efflux-mediated resistance mechanisms, highlights recent nanotechnology developments to design and formulate nanobiotics, and examines their potential to inhibit efflux pumps in multidrug-resistant bacterial strains. By targeting efflux systems, nanobiotics offer a potent and innovative approach to restoring the efficacy of conventional antibiotics and advancing the treatment of multidrug-resistant bacterial infections.

Keywords:  Antibiotic resistance; efflux-mediated resistance; nanobiotics; nanocarriers; resistance nodulation cell division (RND)

DOI:  https://doi.org/10.1080/1040841X.2025.2597220
Brief Bioinform. 2025 Nov 01. pii: bbaf619. [Epub ahead of print]26(6):

In silico approaches for discovering microbial antiviral defense systems.

Lixu Jiang, Yansheng Li, Baocai Xie, Lianrong Wang, Shi Chen.

  Prokaryotes possess a remarkably diverse and dynamic repertoire of antiviral defense systems, enabling them to withstand phage predation. However, their frequent horizontal gene transfer, extensive sequence diversity, modular genomic organization, and rapid evolution make purely experimental discovery challenging. Coupled with the massive influx of microbial genomes from high-throughput sequencing, computational strategies have become indispensable complementary tools that can enhance the efficiency and scope of defense systems discovery. In this review, we categorize computational approaches into four major strategies: (i) Sequence homology-based methods, which reliably annotate known defense systems through protein sequence similarity but are limited in detecting highly divergent or novel systems; (ii) Structure-guided approaches, which leverage conserved protein folds to uncover remote homologs and single-gene defense proteins, providing sensitivity beyond sequence-based identification, albeit at high computational cost; (iii) Genomic context-based strategies, which exploit gene co-localization and defense islands to uncover multi-gene defense clusters and previously uncharacterized defense modules; and (iv) Artificial intelligence-powered methods, which integrate sequence-derived embeddings with genomic context information to predict low-homology proteins and reconstruct candidate defense systems at scale, enabling discovery of novel systems beyond the reach of conventional approaches. We further discuss emerging tools and frameworks, such as the conserved gene cluster discovery tool and genomic foundation models, which hold strong potential to extend conventional approaches for identifying novel defense systems and supporting the generative design of synthetic modules. By comparing methodological principles, strengths, and limitations, this review provides a practical framework for the systematic exploration of microbial immune systems, guiding applications such as rational phage therapy, microbiome engineering, and synthetic biology.

Keywords:   in silico discovery; antiviral defense systems; artificial intelligence; bacterial immunity; defense islands

DOI:  https://doi.org/10.1093/bib/bbaf619
Int Wound J. 2025 Dec;22(12): e70795

Biofilm in Diabetic Foot Ulcers: A Systematic Narrative Review.

George Theodorakopoulos, David G Armstrong.

Biofilms are a key driver of chronicity and treatment failure in diabetic foot ulcers (DFUs), yet clinical evidence quantifying their impact and management remains fragmented. This systematic narrative review synthesised recent evidence (2015-2025) on the prevalence, diagnostics, and management of biofilm in DFUs. A Systematic Review of the Literature (SRL) was conducted following PRISMA 2020 guidelines across PubMed/MEDLINE, Scopus, Cochrane Library and ScienceDirect. Eligible studies included adults with DFUs reporting biofilm/bioburden metrics or interventions aimed at biofilm disruption. Risk of bias was assessed using RoB 2 for randomised trials and ROBINS-I for non-randomised studies. Data were narratively synthesised by evidence tier (Tier 1 = clinical; Tier 2 = preclinical/mechanistic). Of 600 records screened, 25 studies met inclusion criteria (Tier 1 n = 9; Tier 2 n = 5; reviews n = 11). Over half of bacterial isolates in DFUs were biofilm producers, with multidrug resistance exceeding 90% in several cohorts. Fungi were detected in 31% of ulcers by qPCR but only 9% by culture. Tier 1 clinical evidence supports standard care components-debridement, antiseptics, and negative-pressure wound therapy-for improved healing, though direct antibiofilm outcomes remain limited. Emerging strategies (enzymatic agents, peptides, cold plasma, smart dressings) show promise in vitro but lack clinical translation. Evidence for direct antibiofilm efficacy in DFUs remains scarce. Current data justify maintaining guideline-based care while prioritising trials that integrate validated biofilm endpoints, standardised microbiological methods, and antifungal components. Distinguishing established from experimental approaches is essential to advancing safe, evidence-based biofilm management in DFUs.

DOI: https://doi.org/10.1111/iwj.70795
Pestic Biochem Physiol. 2026 Jan;pii: S0048-3575(25)00445-6. [Epub ahead of print]216(Pt 1): 106732

Combined application of novel broad-spectrum bacteriophages and antagonistic bacterial strain: enhanced biocontrol efficacy against Streptomyces induced potato common scab.

Xiaohan Xu, Cancan Zhu, Xiaoxiao Guo, Qing Shi, Xiaoqing He, Yi Jin.

  Potato common scab (PCS), caused by pathogenic Streptomyces spp., is a globally significant disease leading to substantial economic losses in potato production. Conventional chemical control methods pose environmental risks and contribute to antibiotic resistance, necessitating sustainable alternatives. This study isolated three novel broad-spectrum bacteriophages (pSt2308, pSt2402, and pSs2407) from potato field soils, exhibiting lytic activity against multiple pathogenic Streptomyces strains while sparing non-pathogenic species. All three phages demonstrated exceptional environmental stability, tolerating temperatures (4-50 °C), pH (3-11), and UV exposure. Whole-genome sequencing revealed that the three phages belong to the class Caudoviricetes, with pSt2308 and pSt2402 identified as new species. Following phage cocktail treatment, in vitro assays demonstrated rapid pathogen lysis, while in vivo experiments on potato slices and radish seedlings showed significant reductions in disease severity and enhanced plant growth. Combined with the antagonistic strain Bacillus cereus BC-1, which exhibited strong inhibition against PCS pathogens, the phage cocktail synergistically enhanced biocontrol efficacy against mixed pathogenic Streptomyces spp. infected potato slices, radish seedlings or contaminated soil. Our findings highlight the synergistic potential of phage-antagonist combinations as an eco-friendly and effective strategy for managing PCS, offering a promising alternative to chemical pesticides.

Keywords:  Streptomyces; biocontrol; broad-spectrum bacteriophage; phage-bacteria synergy; potato common scab

DOI:  https://doi.org/10.1016/j.pestbp.2025.106732
Synth Syst Biotechnol. 2026 Jun;12 59-70

Defect-complementation homologous recombination: A novel strategy for precise genome engineering of virulent phages.

Hailin Zhang, Yueyue Song, Wenyue Liu, Xiaoqing Zheng, Xiaodong An, Chao Li, Weihua Chen, Hailong Wang, Yuran Zhang.

  Engineered bacteriophages (phages) have been developed to overcome the limitations of natural phage therapies and serve as precision-targeted agents against drug-resistant bacterial infections. However, their application has been constrained by the low efficiency of existing genome-editing tools, largely because of the absence of effective selection markers. This study proposed a novel strategy, termed defect-complementation homologous recombination (DCHR), for precise phage genome editing. In this approach, CRISPR-Cas9 cleaves a donor plasmid in host cells to release a linear donor template carrying homology arms, an essential phage gene used as a selection marker, and two lox sites. The donor template undergoes homologous recombination with the genome of essential gene-deficient phage, thereby enabling targeted genome modifications. Using DCHR, we successfully generated large genomic deletions (1.48-kb gp0.4-0.7 and 1.02-kb gp4.3-4.7), achieved gene insertion (3.08-kb lacZ), and introduced a single-base substitution (TGA to TAA) in the stop codon of gp9 within the same T7 phage genome, all with 100 % accuracy. The significant advantages of DCHR are as follows: (i) High-efficiency screening: Only progeny phages derived from successful homologous recombination retain viability and replicative capacity, thereby greatly simplifying recombinant isolation. (ii) Editing flexibility: Unlike CRISPR-Cas systems, DCHR cannot be constrained by protospacer adjacent motif dependence and allows modifications across diverse genomic loci. (iii) High recombination efficiency: DCHR can achieve a recombinant phage titer of 3.1 × 105 PFU mL-1 (plaque-forming units per mL) without relying on exogenous homologous recombination systems. In summary, DCHR demonstrates potential as a precise and efficient general genome-editing tool that facilitates design of engineered phages and advances functional genomic studies.

Keywords:  Cre-lox; Genetic complementation; Homologous recombination; Phage genetic manipulation; Phage genome engineering

DOI:  https://doi.org/10.1016/j.synbio.2025.11.002
Mol Immunol. 2025 Dec 04. pii: S0161-5890(25)00278-0. [Epub ahead of print]189 119-132

Immunological pathways triggered by Porphyromonas gingivalis in periodontitis: New insights into molecular mechanisms.

Klara Ferenc, Anna Bożek, Katarzyna Gawron.

  Periodontitis (PD) is one of the most common chronic inflammatory diseases worldwide. One of the keystone causative agents of PD is considered an anaerobic, Gram-negative, opportunistic oral bacterium - Porphyromonas gingivalis, which has evolved sophisticated mechanisms to evade host immune responses, thus contributing to persistent inflammation and periodontal tissue destruction. As reported in the literature, P. gingivalis interacts with various host receptors and manipulates key immunological signaling pathways, including Toll-like receptor (TLR) signaling, the complement system, and PI3K-AKT signaling. By disrupting these pathways, it subverts host defense mechanisms, promotes dysbiosis, and exacerbates PD progression. Furthermore, emerging evidence suggests, that P. gingivalis infections may have systemic implications, linking PD to conditions, such as, neurodegenerative disorders, rheumatoid arthritis, and cardiovascular diseases. We discussed in this review the molecular mechanisms by which P. gingivalis manipulates key signaling pathways of inflammation and provided a comprehensive review of the intricate molecular interactions between P. gingivalis and host immune responses, emphasizing the ability of this oral pathogen to alter fundamental signaling cascades. Continued exploration of the molecular interplay between this pathogen and the host immune system will not only enhance our knowledge of PD but may also have broader implications for understanding pathogenetic events of associated systemic inflammatory conditions.

Keywords:  Complement system; Immune evasion; Inflammation; P. gingivalis; PI3K-AKT signaling; Periodontitis; Toll-like receptors

DOI:  https://doi.org/10.1016/j.molimm.2025.12.001
Curr Opin Ophthalmol. 2025 Dec 02.

Eying up predatory bacteria: living antimicrobials for ocular infections.

Robert M Q Shanks, Eric G Romanowski, Dhara R Patel, Daniel E Kadouri.

   PURPOSE OF REVIEW: The growing threat of antibiotic-resistant pathogens, particularly in ocular infections like bacterial keratitis, necessitates alternative therapeutic strategies. This review evaluates the potential therapeutic role of predatory bacteria as novel live antimicrobials, offering a timely exploration of their potential in overcoming resistance mechanisms such as biofilm formation and persister cell development.
RECENT FINDINGS: Predatory bacteria, including Bdellovibrio bacterovorus and Micavibrio aerguinosavorus selectively target Gram-negative bacteria, including Pseudomonas aeruginosa, while sparing Gram-positive ocular surface. They exhibit rapid bactericidal activity and efficacy against biofilms, persister cells, and antibiotic-resistant pathogens, but induce little inflammation. Advances in storage and delivery methods, such as lyophilization, cryomicroneedles, and thermoresponsive hydrogels, have potential to increase their therapeutic feasibility. However, in-vivo efficacy remains variable and their narrow spectrum limits effectiveness against Gram-positive pathogens.
SUMMARY: Predatory bacteria present a promising alternative to traditional antibiotics in ocular therapeutics, particularly for drug-resistant infections. Integration of predatory bacteria with bacteriophages or conventional antibiotics may further optimize their potential. Continued translational research is essential to address current limitation and to validate their safety and efficacy for human or veterinary applications.

Keywords:  ; antibiotic resistance; endophthalmitis; keratitis; predatory bacteria

DOI:  https://doi.org/10.1097/ICU.0000000000001200
Health Sci Rep. 2025 Dec;8(12): e71564

Dysbiosis and Therapeutic Modulation of the Gut Microbiota in Multiple Sclerosis: A Narrative Review.

Mojtaba Memariani, Hamed Memariani.

   Background and Aims: Multiple sclerosis (MS) is a persistent autoimmune disease that affects the central nervous system. The etiology of MS is complex, involving a variety of genetic and environmental factors. Mounting evidence suggests that dysbiosis significantly impacts the progression of MS mainly through its direct effects upon the immune system. Given the vital connection between the gut microbiota and immune health, particularly in the context of autoimmune diseases, this review aims to summarize the existing knowledge regarding alterations in the gut microbiota among MS patients, with a focus on microbiota-based therapeutic approaches.
Methods: A detailed literature review was carried out to gather contemporary evidence on dysbiosis of the gut microbiota in MS patients. Furthermore, studies dealing with the modification of gut microbiota for therapeutic applications in MS have been included.
Results: A distinct variation in specific bacterial phyla, orders, families, and genera, as well as metabolites, was found in MS patients. Exploring therapeutic options such as antibiotics, probiotics, dietary interventions, fecal microbiota transplantation, phage therapy, and helminth therapy may present valuable opportunities for gut microbiota modification in MS treatment.
Conclusion: Altering the gut microbiota in patients with MS may serve as a potentially effective treatment strategy. Nevertheless, future research should prioritize the standardization of these therapies. Finally, it is imperative that researchers concentrate on large-scale studies or trials to scrutinize the practical relevance of these therapeutic options.

Keywords:  diet; dysbiosis; gut microbiota; multiple sclerosis; probiotics

DOI:  https://doi.org/10.1002/hsr2.71564
Adv Mater. 2025 Dec 06. e15854

Self-Adaptive Wound Dressings for Wound Healing and Repair.

Xin Zhao, Huiru Xu, Yuchen Sun, Yutong Yang, Baolin Guo.

  Skin plays critical roles in defending against external threats and maintaining homeostasis. However, wound repair is frequently impeded by infection, oxidative stress, and chronic inflammation, especially in pathological conditions. Traditional dressings offer passive protection but lack responsiveness to the evolving wound environment. Self-adaptive wound dressings dynamically interact with wound microenvironments, exhibiting stimuli-responsiveness, controlled therapeutic release, mechanical adaptability, and multifunctional bioactivities, thereby offering tailored support across diverse stages of wound repair. This review provides a comprehensive overview of self-adaptive wound dressings, beginning with the biological basis of skin repair and factors that impede healing in chronic wounds. Traditional and self-adaptive dressings are compared, emphasizing advances in material design, structural engineering, and functional integration. Recent advances in key platforms, including hydrogels, films, sponges, microneedles, nanofibers, wearable biosensors, and nano/microparticle-based systems, are critically evaluated for their roles in managing acute, chronic, and complex wounds. Finally, current challenges in clinical translation, including biosafety, scalability, and personalization, are highlighted, and future directions for intelligent wound care are proposed. This review aims to inform the rational design of advanced self-adaptive wound dressings and promote their integration into precision wound therapy.

Keywords:  hydrogel wound dressings; multifunctional dressings; self‐adaptive dressings; stimuli‐responsive; wound microenvironment

DOI:  https://doi.org/10.1002/adma.202515854
JMIR Res Protoc. 2025 Dec 02. 14 e79652

Virtual Wound Care in Australian Nursing Homes: Protocol for a Pilot and Feasibility Study.

Heather Russell, Annie Banbury, Katherine Smith, Michelle Barakat-Johnson, Meredith Makeham, Georgina Luscombe.

   Background: Chronic wounds, those which have not healed in a timely manner, are a significant health and economic burden. Older people, especially those living in nursing homes, are disproportionately affected by chronic wounds, and effective management and prevention is a persistent challenge. Specialized wound care can improve outcomes; however, access is limited by aged care workforce shortages, fragmented care, and lack of local services, especially in rural and nursing home settings. Virtual wound care interventions such as WoundView (Coviu Global Pty Ltd), a novel computer vision-based artificial intelligence wound analysis app embedded in Coviu's existing telehealth platform, offer a potential solution to enhance engagement with specialized wound care services.
Objective: This protocol aims to outline a pilot and feasibility study for WoundView to assess the acceptability and feasibility of the intervention in preparation for a planned implementation study. The pilot and feasibility study will estimate recruitment and retention rates along with protocol adherence and adaptations. Qualitative exploration of the acceptability of recruitment processes, training and education, participant assessments, intervention delivery, and secondary outcome measures will inform the development of an implementation study of WoundView.
Methods: The WoundView pilot and feasibility study is a prospective, nonrandomized study in 2 nursing homes in New South Wales, Australia. The research population will comprise up to 10 nursing home residents, 10 to 30 nursing home staff, and 10 wound care clinicians. All resident participants will receive the intervention, WoundView, as routine clinical care throughout the study period. Virtual care will be conducted with a specialized wound care clinic using WoundView's wound analysis and telehealth features to guide the clinical management of chronic wounds. Wound measures, health-related quality of life, virtual care activity, hospitalization rates, health resource use case studies, and participant satisfaction will be assessed. Nursing home staff and wound care clinicians' satisfaction with WoundView will be collected through brief surveys and in-depth interviews.
Results: The WoundView pilot and feasibility study was approved by the university's ethics committee and registered on the Australian New Zealand Clinical Trial Registry. Recruitment and enrollment for the study began in May 2025. Results are expected in the second half of 2025.
Conclusions: The design and implementation of virtual care interventions in nursing homes is an underinvestigated issue. Outcomes from this study will contribute to the design of an implementation study testing WoundView in a range of nursing homes around Australia. The integration of WoundView is expected to transform the use of virtual care for wound management and lead to earlier intervention and increased access to specialist wound advice services for nursing home residents.

Keywords:  chronic wound; homes for the aged; nursing homes; pilot and feasibility study; telehealth; virtual care

DOI:  https://doi.org/10.2196/79652
J Oral Microbiol. 2025 ;17(1): 2589648

The oral microbiome in aging: a window into health and longevity.

Zijun Yue, Chunhao Li, Fangxu Yan, Shuwen Guan, Yue Fan, Xingming Chen.

   Background: Aging is characterized by progressive physiological decline and increased susceptibility to age-related diseases. The oral microbiome, a complex community of microorganisms, has been increasingly recognized as a potential key player in the aging process.
Objective: This review aims to explore and summarize the relationship between the oral microbiome and aging, with a specific focus on contrasting microbial changes in healthy and unhealthy aging populations.
Design: We conducted a comprehensive review of the current literature to synthesize evidence on oral microbiome shifts during aging, the influencing factors, associations with age-related conditions, and potential interventions.
Results: Evidence indicates that the composition of the oral microbiome changes with age, although findings on diversity are inconsistent, with reports of both increases and decreases in older adults. These shifts are influenced by factors such as diet, oral hygiene, and immune function. Unhealthy aging, including conditions like frailty, neurodegenerative diseases, and sarcopenia, is associated with distinct oral dysbiosis. Potential mechanisms linking the oral microbiome to aging include chronic inflammation and immunosenescence. Interventions targeting the oral microbiome, such as probiotics and dietary modifications, show promise in promoting healthspan.
Conclusions: The oral microbiome is significantly altered during aging and is implicated in age-related health status. It represents a promising target for strategies aimed at promoting healthy aging. Future research should prioritize elucidating the functional mechanisms of oral microbiota and developing targeted microbiome-based interventions.

Keywords:  Microbiology; aging; frailty; gerontology; immunosenescence; inflammation; oral microbiome

DOI:  https://doi.org/10.1080/20002297.2025.2589648
J Dairy Res. 2025 Dec 05. 1-13

Characterization of bacteriophages infecting Escherichia coli associated with bovine mastitis.

Sashikanta Parida, Nagendra R Hegde.

  Bovine mastitis poses a significant threat to dairy production worldwide. Among the various etiologies of mastitis, Escherichia coli is a predominant environmental pathogen. Antibiotic-resistant E. coli poses substantial challenges for treating mastitis and is a threat to public health, necessitating the exploration of alternative therapeutic strategies. We studied bacteriophages as a potential alternative therapy for bovine mastitis-associated E. coli. We isolated 37 bacteriophages infecting E. coli, and characterized them for host range, growth kinetics, morphology, stability, genome fingerprinting and genome sequencing and analysis. The phages lysed between 4% and 62% of the E. coli isolates tested. Notably, 30 phages lysed bovine mastitis-associated strains. The 10 best phages selected based on host strain specificity revealed latent periods ranging from 50 to 90 min and burst sizes between 7 and 69 PFU/mL. Based on their shorter latent period and larger burst size, seven phages were subjected to transmission electron microscopy, which revealed their myovirus and siphovirus morphologies. Restriction fragment length polymorphism (RFLP) analysis of the same seven phages indicated six different patterns. The seven phages were stable at temperatures ranging from 4°C to 50°C, and at pH values ranging from 3 to 9. Whole-genome sequencing and analysis of the six phages, which showed unique RFLP patterns, predicted a lytic lifecycle, with no sequences encoding toxins or antibiotic-resistance genes. Importantly, these six phages were able to lyse multidrug-resistant and extended β-lactamase (ESBL)-producing E. coli under in vitro conditions and mastitis-associated E. coli in milk. Additionally, three phages belonging to different genera did not exhibit toxicity to mammalian cells. This study underscores the potential of bacteriophages as alternative therapeutic agents for E. coli-associated bovine mastitis. Our study has broader implications for udder and animal health, as well as the production of quality milk and dairy products, and food safety and security.

Keywords:  Bacteriophage; Escherichia coli; genome analysis; lytic activity; stability

DOI:  https://doi.org/10.1017/S0022029925101349
Clin Transl Sci. 2025 Dec;18(12): e70430

Cell and Gene Therapy: Transforming Treatment Paradigms for Patient-Centric Care.

Sojeong Yi, Chia-Yung Wu, Avery McIntosh, Maria E Santaella, Tara M Robinson, Michael Z Liao.

  Cell and gene therapies (CGTs) are transforming medicine by offering potential cures for diseases previously considered untreatable. Despite rapid advancements, challenges remain in optimizing efficacy and safety and ensuring patient accessibility and preference due to high costs and clinical uncertainties, particularly for rare diseases and one-time administration. The American Society of Clinical Pharmacology & Therapeutics (ASCPT) held a CGT satellite conference in 2025, titled "Cell and Gene Therapy: Transforming Treatment Paradigms for Patient-Centric Care." This manuscript summarizes the conference, covering gene therapies and T-cell immunotherapies from scientific, clinical, and patient-centered perspectives. Key topics on gene therapy included "platformization" to streamline development, lessons from adeno-associated virus-based gene therapies for hemophilia from patient and clinical perspectives, clinical pharmacology, and model-informed drug development (MIDD) considerations. The conference also highlighted T-cell immunotherapies including chimeric antigen receptor T therapy (CAR T), focusing on factors affecting cellular kinetics, efficacy, and safety, as well as emerging allogeneic CAR T for autoimmune diseases and MIDD strategies to optimize therapy design and clinical outcomes.

Keywords:  cell‐ and tissue‐based therapy; gene editing; genetic therapy; immunotherapy; model informed drug development

DOI:  https://doi.org/10.1111/cts.70430
Front Artif Intell. 2025 ;8 1718436

Artificial intelligence for surgical data management and decision support: lessons from wound care.

Esteban Zavaleta-Monestel, Sebastián Arguedas-Chacón, Katherine Cordero-Bermúdez.



Keywords:  artificial intelligence; clinical decision-making; health care; natural language processing; outcome assessment; wound healing

DOI:  https://doi.org/10.3389/frai.2025.1718436
Hematology Am Soc Hematol Educ Program. 2025 Dec 05. 2025(1): 659-667

Deconstructing gene therapy in hemophilia for the clinician.

Guy Young.

After decades of research, gene therapy for hemophilia is now commercially available for both hemophilia A and B. Currently, two products, valoctocogene roxaparvovec (for hemophilia A) and etranacogene dezaparvovec (for hemophilia B), have been licensed following approval in the United States and several other countries. Therefore, clinicians must familiarize themselves with these novel treatment options just as they do with other newly available products in order to provide their patients the opportunity to consider which treatment may suit them best. Undoubtedly, gene therapy is a novel platform for treating human disease, and unlike other hemophilia treatments, its biology, mechanisms, and administration logistics are quite complex. Furthermore, additional products using different approaches have entered clinical trials, with more in the preclinical stages of development. This review's aims are (1) to deconstruct gene therapy in hemophilia and provide a basic framework for understanding its components and processes, including the transgene, the vector, and the delivery systems, in order to help clinicians present gene therapy as a treatment option in a shared decision-making model, better understand the clinical data, and explain gene therapy to their patients; (2) to gain knowledge of the currently approved gene therapies for hemophilia A and B, including their eligibility and exclusion criteria and the range of expected outcomes; and (3) to comprehend the shared decision-making process for these therapies and their implementation in clinical practice. In addition, a brief review of the currently approved products and those in clinical trials is presented, followed by a discussion of practical considerations for implementing gene therapy in practice.

DOI: https://doi.org/10.1182/hematology.2025000763
Trends Microbiol. 2025 Dec 03. pii: S0966-842X(25)00354-3. [Epub ahead of print]

Opportunities and challenges in applying microbiota to clinical cancer immunotherapy.

Dingjiacheng Jia, Liangjing Wang.

  Fundamental research has elucidated the indispensable role of gut microbiota in modulating cancer immunotherapy efficacy. Despite promising preclinical findings, few related approaches have reached clinical trials. In this opinion, we provide insights based on current clinical trials using fecal microbiota transplant or specific bacterial strains as adjuvants to enhance immune checkpoint blockade therapy. We also systematically analyze the challenges in trial design, with a focus on donor selection, patient enrollment, implantation procedures, antibiotic use, safety assessment, and endpoint evaluation. Moving forward, we offer a comprehensive '4D' framework (diversity, diffusion, depth, and delicacy) for accelerating the bench-to-bedside translation. It is hoped that this opinion will help researchers and clinicians aiming to harness microbiome-based strategies to improve cancer immunotherapy outcomes.

Keywords:  cancer immunotherapy; clinical trials; fecal microbiota transplantation; gut microbiota; immune checkpoint blockade

DOI:  https://doi.org/10.1016/j.tim.2025.11.011
Cureus. 2025 Nov;17(11): e95912

Microbiology of Pressure Ulcers: A Systematic Review.

Dmitry Shelepenko, Beatriz Jardim, Luís M Almeida, José Miguel Azevedo, Inês Catalão, Miguel Sítima, Gonçalo Tomé.

  Pressure ulcers are complex wounds frequently complicated by infection. This review aims to characterize the distribution of microorganisms in pressure ulcers and secondarily to assess heterogeneity across studies and compare yields between invasive (biopsies) and noninvasive (swabs/irrigation-aspiration) sampling techniques with implications for antimicrobial management. PubMed, Embase, and the Cochrane Library were searched up to 1 January 2025. Original research articles reporting microbiological data from pressure ulcers were included. Studies were excluded if data were incomplete, combined with other wound types, or derived from non-ulcer sampling sites. Risk of bias was assessed using Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) V2, ROBINS-E, and RoB 2 frameworks. Data were synthesized descriptively and statistically. Twenty-eight studies (1,473 patients, 1,682 pressure ulcers, and 4,231 microbial isolates) were included. The most frequently isolated microorganisms were Staphylococcus aureus (39.7% of ulcers), Corynebacterium spp. (28.8%), Escherichia coli (23.1%), Proteus spp. (23.1%), Streptococcus spp. (22.7%), coagulase-negative Staphylococcus (21.6%), Enterococcus spp. (20.7%), Pseudomonas spp. (17.8%), and Bacteroides spp. (16.0%). On average, 2.5 isolates were reported per ulcer (range: 0.5-4.8). Significant heterogeneity was observed across studies for nearly all major organisms (global heterogeneity: χ² = 1958.4, df = 405, p < 0.001). Swabs more frequently yielded Providencia spp., Pseudomonas spp., Proteus spp., and Enterobacter spp., whereas biopsies more frequently yielded Streptococcus spp., Enterococcus spp., and Klebsiella spp. Comparability was limited by the inclusion of diverse populations treated across 14 different countries over the past 50 years. Methodological inconsistencies in sampling and reporting (particularly regarding contaminants, duplicates, and anaerobes) further complicated interpretation and underscore the need for standardized protocols. Nevertheless, findings consistently confirmed a polymicrobial flora dominated by a small group of recurrent species. The ulcer microenvironment is dynamic and distinct from culture media, complicating both diagnosis and treatment. Despite marked heterogeneity, the consistent predominance of Staphylococcus aureus, Enterobacteriaceae, Streptococcus spp., Enterococcus spp., Pseudomonas spp., and Bacteroides spp. provides a valuable framework for empiric therapy. The potential benefits of short perioperative courses of broad-spectrum antibiotics targeting these pathogens warrant further investigation, and prospective controlled trials are urgently needed. The study protocol was registered in PROSPERO (CRD420251076473) and is available at https://www.crd.york.ac.uk/PROSPERO/view/CRD420251076473.

Keywords:  antibiotic therapy; chronic wounds; microbiology; pressure ulcers; wound infection

DOI:  https://doi.org/10.7759/cureus.95912
Bioinformatics. 2025 Dec 01. pii: btaf649. [Epub ahead of print]

MetaMDA: explainable prediction of microbe-drug association utilizing random walks on a microbe-metabolite-drug heterogeneous network.

Qi Wang, Shuting Chen, Xintian Miao, Yuntao Liu, Bingqiang Liu.

MOTIVATION: Human-associated microbes play a critical role in physiological processes and disease development, including cancer. Predicting microbe-drug associations (MDAs) can aid drug discovery and personalized medicine. However, existing methods cannot predict MDAs involving microbes or drugs absent from labeled data, and they fail to model the underlying biological mechanisms between microbes and drugs. To address these limitations, we propose a novel computational framework, named MetaMDA, for predicting MDAs by performing random walks on a microbe-metabolite-drug heterogeneous network. MetaMDA first constructs a heterogeneous graph that integrates microbes, metabolites, and drugs, enabling the modeling of complex biological interactions. A random walk algorithm with tailored transition probabilities is subsequently applied to the graph, effectively capturing features from multiple node types on a unified scale.
RESULTS: Experimental results across multiple datasets demonstrate that MetaMDA consistently outperforms state-of-the-art methods, achieving an average improvement of 26%. Notably, we show MetaMDA's unique ability to predict MDAs involving microbes or drugs absent from labeled data, as illustrated by associations related to acarbose. Furthermore, mechanistic analysis of MetaMDA provides biological explanations for the associations between E. coli and escitalopram, highlighting its potential to reveal a deeper mechanistic understanding of microbe-drug associations.
AVAILABILITY AND IMPLEMENTATION: The code and datasets are available on Zenodo https://doi.org/10.5281/zenodo.17348446 and GitHub https://github.com/wqlyt17/MetaMDA.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

DOI: https://doi.org/10.1093/bioinformatics/btaf649
BioDrugs. 2025 Dec 02.

Recombinant Molecules as a New Frontier in Mucositis Therapy.

Luís Cláudio Lima de Jesus, Rhayane Cristina Viegas Santos, Vasco Azevedo.

Mucositis significantly impairs patients' quality of life, and despite its clinical importance and the availability of symptomatic treatments, no gold-standard therapeutic protocol has been established. Recent advances in biotechnology and molecular biology have enabled the development of genetically engineered probiotic strains capable of producing or delivering therapeutic molecules directly to inflamed mucosal sites. Although several recombinant biotherapeutic bacteria have advanced to clinical evaluation, most have not yet reproduced the efficacy observed in preclinical models, and no products have yet been commercially approved for human use. This is the first review to comprehensively outline the recombinant molecules as an innovative biotherapeutic option for mucosal inflammation induced by chemoradiotherapy. In this review, we describe how genetically modified bacteria function as living drug delivery platforms, focusing on their ability to produce or deliver recombinant molecules, including antimicrobial peptides, antioxidant enzymes, growth factors, and interleukin receptor antagonists, for mucositis therapy. We further discuss key limitations, including biosafety, control of gene expression, and gut protection levels, while outlining future challenges.

DOI: https://doi.org/10.1007/s40259-025-00758-6
Annu Rev Immunol. 2025 Dec 05.

Harnessing the Microbiome in Cancer Immunotherapy: Regulation, Prediction, and Therapeutic Targeting.

Hassane M Zarour, Giorgio Trinchieri.

Humans are metaorganisms, composed of both host (human) cells and a roughly equal number of commensal microorganisms-collectively known as the microbiome-residing primarily at epithelial barrier surfaces. This review considers human cancer as a disease of the metaorganism, to which the microbiome contributes by influencing genome stability, tissue organization, inflammation, immunity, tumor initiation and promotion, metastasis formation, and therapeutic response. We summarize evidence demonstrating that machine learning models trained on patients' microbiome features moderately predict clinical response to immunotherapy and the development of immune-related adverse events. We review results from single-arm and randomized clinical trials wherein fecal microbiome transplantation from therapy-responsive patients or healthy donors, when combined with therapy targeting programmed cell death 1 (PD-1), improved outcomes in PD-1-refractory patients or served as an effective first-line intervention. We conclude by highlighting the emerging opportunities and ongoing challenges in leveraging the microbiome to enhance the efficacy and safety of cancer immunotherapy.

DOI: https://doi.org/10.1146/annurev-immunol-082323-114522
J Hosp Infect. 2025 Nov 28. pii: S0195-6701(25)00394-9. [Epub ahead of print]

Incisional Negative Pressure Wound Therapy After Inguinal Vascular Surgery Reduction SSI and Mortality: A Systematic Review and Meta-analysis.

Ibrahim Moqbel, Youssef Z Farhat, Alaa R Al-Ihribat, Ahmed Oun, Mohamed F Srour, Yahya A Mahmoud, Mario D'Oria.

   BACKGROUND: Surgical site infections (SSIs) are common after inguinal vascular surgery, affecting up to 44% of patients and substantially increasing morbidity, mortality, and cost. Although peri-operative antibiotics reduce SSIs, the benefit of adjunctive measures remains uncertain. Incisional negative-pressure wound therapy (NPWT) has been proposed to decrease infection risk, but its efficacy-particularly against severe infections-remains debated.
METHODS: PubMed, Scopus, Web of Science, and Embase were searched for randomized and cohort studies published between 2005 and 2025 comparing NPWT with standard wound care in inguinal vascular surgery. Primary outcome was SSI defined by CDC criteria or Szilagyi classification. Secondary outcomes included complications, mortality, reoperation, readmission, operative time, and hospital stay. Risk of bias was evaluated with ROBINS-I and RoB 2. Pooled estimates were calculated using random-effects models; heterogeneity evaluated by Chi-square and I2 statistics.
RESULTS: Twenty-one full-text studies and one conference abstract (4,125 patients) were included. NPWT significantly reduced overall SSI (RR 0.52; 95% CI 0.42-0.64; p < 0.001), total complications (RR 0.68; 95% CI 0.57-0.81; p < 0.001), mortality (RR 0.48; 95% CI 0.30-0.77; p = 0.002), and seroma/lymphatic events (OR 0.58; 95% CI 0.38-0.91; p = 0.02) with low-to-moderate heterogeneity. Benefit was greatest in bilateral incisions. No significant differences were observed for hematoma, wound dehiscence, amputation, operative time, length of stay, reoperation, or readmission.
CONCLUSIONS: NPWT significantly reduces superficial and overall SSIs, complications, and mortality after inguinal vascular surgery, particularly in bilateral procedures. Evidence for deep infection prevention is limited, and further high-quality randomized trials are required to optimize patient selection and implementation.

Keywords:  CDC criteria; Negative pressure wound therapy (NPWT); Surgical site infection (SSI); Szilagyi classification; Vascular surgery; Wound complications; Wound healing; inguinal vascular surgery

DOI:  https://doi.org/10.1016/j.jhin.2025.11.021
Radiol Cardiothorac Imaging. 2025 Dec;7(6): e250041

Quantitative Imaging for Interstitial Lung Disease.

Cody M Anderson, Roshan Singh, Chi Wan Koo.

  Quantitative imaging has emerged as a promising tool for the diagnosis, classification, and prognostication of interstitial lung disease (ILD). Both global and regional lung abnormalities can be objectively and reproducibly measured using quantitative imaging, which is particularly useful for early disease evaluation and assessment of subtle changes. Accurate ILD classification and identification of inconspicuous changes allow for more personalized treatment decisions and, ultimately, improved patient outcomes. Because CT is the primary imaging modality for ILD evaluation, most of the computer-aided support systems have been developed for this modality and are referred to as quantitative CT. While CT continues to advance with functional capability using dual-energy technology, new MRI techniques are being developed that offer the ability to further improve ILD evaluation. Recent advancements in the field of artificial intelligence underly the development of these new quantitative imaging tools. As quantitative imaging for ILD evaluation becomes more common, it will likely play an increasingly important role in the general clinical radiology workflow, necessitating a familiarity of its use for the general radiologist. This review summarizes current applications of quantitative CT in the evaluation of fibrotic ILDs, including idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, and connective tissue disease-related ILD, and highlights emerging quantitative MRI techniques for ILD assessment. Keywords: Applications-CT, Deep Learning, Machine Learning, Radiomics, CT-Quantitative, Thorax, Lung © RSNA, 2025.

Keywords:  Applications-CT; CT-Quantitative; Deep Learning; Lung; Machine Learning; Radiomics; Thorax

DOI:  https://doi.org/10.1148/ryct.250041
J Wound Care. 2025 Dec 02. 34(12): 1000-1006

The effect of autologous platelet-rich plasma on donor site wound healing: a randomised crossover clinical trial.

Uranus Dasmeh, Ali Akbar Mohammadi, Raha Shahrokhi, Sara Shahriarirad, Reza Shahriarirad, Reyhaneh Naseri.

   OBJECTIVE: This study aimed to investigate whether application of autologous platelet-rich plasma (PRP) at split-thickness skin grafting (STSG) donor sites in patients with burns can promote wound healing.
METHOD: A randomised crossover clinical trial was conducted involving participants, each with a donor site divided into two equal-sized areas for application of PRP and Vaseline gauze (VG) or with VG alone. Wound healing progress was evaluated at days 14, 21 and 30 postoperatively by measuring the healed area and comparing it between the PRP and VG groups.
RESULTS: The study included 20 participants, equally divided into the two groups. Both groups demonstrated significant improvement throughout the study period. The PRP group demonstrated a statistically significant acceleration in wound healing compared to the control group, at days 14 and 21 postoperatively. However, at 30 days' postoperatively, there was no statistically significant difference in healed area between the two groups.
CONCLUSION: The findings of this study suggest that PRP has the potential to expedite the healing process and may help reduce hospital stay and wound infection rates, even though it did not result in a significantly larger overall healed area. The decision to use PRP should take into account various factors including resources, costs and desired clinical outcomes. Future research is needed to elucidate the role of PRP in the treatment of donor wounds.

Keywords:  Vaseline gauze; autologous; burns; platelet-rich plasma; wound; wound care; wound dressing; wound healing

DOI:  https://doi.org/10.12968/jowc.2023.0210
Cureus. 2025 Oct;17(10): e95492

Failure of Empirical Antimicrobial Therapy in Diabetic Foot Ulcer With Chronic Osteomyelitis: A Case Report.

Melike Karabulut Ozer.

  Diabetic foot infections (DFIs) are frequent and severe complications of diabetes mellitus that can lead to chronic wounds, osteomyelitis, and even limb amputation if not properly managed. This case report describes the clinical consequences of prolonged empirical antibiotic therapy without culture guidance in a patient with a diabetic foot abscess. A 72-year-old man with type 2 diabetes and hypertension presented with a chronic, non-healing deep foot abscess after receiving 15 consecutive courses of empirical oral antibiotics over eight months. Magnetic resonance imaging suggested osteomyelitis of the fifth metatarsal bone. Urgent surgical drainage and tissue cultures revealed Escherichia coli and Pseudomonas aeruginosa, both resistant to multiple commonly used antibiotics but susceptible to ceftriaxone and carbapenems. Targeted intravenous therapy with ceftriaxone and metronidazole led to rapid improvement within one week and complete healing by the third month. This case emphasizes that prolonged empirical therapy may lead to treatment failure and antimicrobial resistance. Early surgical intervention combined with culture-guided antibiotic selection is crucial for effective management of DFIs and for preventing severe complications such as amputation. This case underscores the importance of multidisciplinary and microbiologically guided approaches.

Keywords:  diabetic foot infection; empirical therapy; multi-drug resistance; osteomyelitis; wound healing

DOI:  https://doi.org/10.7759/cureus.95492
J Nucl Med Technol. 2025 Dec 04. 53(Suppl 1): 49S-52S

Theranostics Education and Training.

Paul M Searfoss.

  The integration of targeted therapies and diagnostic imaging has significantly advanced the field of nuclear medicine. This article highlights the critical importance of comprehensive training and education in theranostics to ensure high-quality patient care and adherence to regulatory standards. Ongoing education is essential for technologists to adapt to evolving clinical practices and supports institutional goals of staff retention. This article presents a structured approach to training, including standard operating procedures, protocols, and competency assessments specific to 177Lu-based therapies. A multidisciplinary strategy involving various health care stakeholders is emphasized as central to the success of theranostic practice. Additionally, the article explores key training and onboarding practices and provides guidance on the use of resources from professional organizations to build staff knowledge and confidence. As theranostics continues to expand in clinical application, maintaining compliance across hospital, state, and federal levels is paramount to advancing safety, quality, and efficiency in nuclear medicine.

Keywords:  competencies; protocol; radiation therapy planning; radionuclide therapy; standard operating procedures

DOI:  https://doi.org/10.2967/jnmt.125.270762