bims-fagtap 2026-04-05 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2026–04–05
thirty-six papers selected by
Luca Bolliger, lxBio

Engineered phages evade the complete defense repertoire of highly phage-resistant MRSA clinical isolates.
Management of Diabetic Foot Infections Using Phage Therapy.
Micrografts-a novel ally in hard-to-heal wounds: a systematic review.
Bacterial composition and healing tendency with cold atmospheric plasma treatment in diabetic wounds.
The repertoire of resistance mutations selected by a Pseudomonas aeruginosa type IV pilus-targeting lytic bacteriophage.
Rapid resistance evolution against phage cocktails.
The neonatal lung microbiome: a dynamic determinant of respiratory health, disease, and novel therapeutics.
Phage characterization analysis in respiratory samples from infected patients based on metagenomic next-generation sequencing.
Characterization of an Indigenous Lytic Phage Targeting Multidrug-Resistant Salmonella enterica.
Metagenome-based insights into bacteriophage diversity of an urban river ecosystem.
Neglected kingdoms: the gut virome, mycobiome and their role in inflammatory bowel disease.
Semantic fusion of dual perspectives on genomic sequences and quorum sensing for bacteriophage lifestyle prediction.
Biofilm spatial structure and superinfection immunity modulate inter-phage competition.
Artificial Intelligence-Enhanced Wound Care to Improve Access, Efficacy, and Equity in Wound Care for Older Adults in Rural and Remote Regions of Canada.
A Review on Models for Wound Healing.
Changes in nutritional priorities and management in people with CF.
Multifunctional nanozyme systems for combating bacterial infections in wound treatment.
[From oral microbiome dysbiosis to renal injury: research advances in the mechanism of association between periodontitis and diabetic kidney disease].
Bacteriophages targeting Acinetobacter baumannii in the era of antibiotic failure: a review.
Secure and accessible AI in nursing education: A modular agentic chatbot framework comparing ChatGPT-4o with an open-source LLM for chronic wound care.
Blueprint for Drug Repurposing Success: Foundational Concepts and Practical Framework.
Biofilm Exoproteins From Staphylococcus Species Impede Re-Epithelialization of Nasal Epithelial Cells During Wound Healing and Cease Ciliary Beat Frequency.
Dismantling S. aureus virulence: Latest advances in toxin neutralization and regulatory network-targeted anti-virulence strategies (2025).
Deep learning-based high-information-content graph representation of early stage bacterial biofilms.
Puberty and Growth in Cystic Fibrosis: A Review.
Systemic antibiotics for diabetes mellitus-related foot infections: an integrative literature review.
Antimicrobial Hydrogel for Diabetic Wound Treatment.
Emerging synthetic biology-assisted technologies for overcoming antibiotic resistance: CRISPR-Cas, bacteriophage, microbiome, and metabolic engineering-based solutions.
Clinical applications of machine learning for infection assessment in diabetic foot ulcers.
Rise of the viral giants: common themes underlying genome gigantism in eukaryotic viruses and bacteriophages.
Effect of periodontal therapy on the oral microbiome and lung function: an intervention study.
Improving Diabetic Foot Care With Infrared Thermography and Artificial Intelligence: A Review.
Pseudomonas aeruginosa lasR mutants resist phagocytosis and alter inflammatory cytokine production by cystic fibrosis macrophages.
Interspecies Biofilm Dynamics Among Staphylococci: Inflammatory Contributions to Chronic Rhinosinusitis.
Pyelonephritis Caused by Pseudomonas aeruginosa: From Treatable Infection to Therapeutic Dead-End, Rescued by an Investigational Antibiotic.
Selection of porin and LPS mutants during infection by phage T4 facilitates the emergence of β-lactam resistance in Escherichia coli.

bioRxiv. 2026 Mar 26. pii: 2026.03.26.714447. [Epub ahead of print]

Engineered phages evade the complete defense repertoire of highly phage-resistant MRSA clinical isolates.

Sarah M Voss, Katharine C King, Devin J Hunt, Adam A Wilson, Bruria Samuel, Orazio R Bagno, Peter F W Sparklin, Bridget Cassata, Joshua W Modell.

Phage therapy is a re-emerging approach for antimicrobial-resistant bacterial infections. However, the narrow host range of most phages remains a major barrier to the success and wider adoption of phage therapy. Although receptor incompatibility is often assumed to define phage-host specificity, we demonstrate that anti-phage defense systems are major determinants of host range in Staphylococcus aureus . Using a methicillin-resistant S. aureus (MRSA) clinical isolate as a model, we characterized the targeting profiles of its 15 defense systems and, for the first time, generated therapeutic phages that evade the full defense repertoire of a multi-phage-resistant strain. In particular, we show that defense-guided phage recombination is a powerful tool that leverages the modular design of phage genomes to replace targeted with untargeted components. Our holistic approach unveils defense synergies that constrain phage evasion and redundancies that allow the simultaneous evasion of multiple defenses. Finally, we show that an engineered phage cocktail prevents the emergence of phage resistance in the model and a second clinical strain with similar defenses. Our work provides a blueprint for translating our expanding knowledge of defense system identity and mechanism into the rational design of effective, next-generation phage therapeutics.

DOI: https://doi.org/10.64898/2026.03.26.714447
Infect Drug Resist. 2026 ;19 577526

Management of Diabetic Foot Infections Using Phage Therapy.

Mohsen Nazari, Leili Shokoohizadeh.

  Diabetic foot infections (DFIs) represent a major and increasing complication of diabetes mellitus, often leading to hospitalization, osteomyelitis, and lower limb amputation. The rising prevalence of multidrug-resistant pathogens in DFIs has limited the effectiveness of conventional antibiotic therapy, emphasizing the need for alternative or adjunctive approaches. Bacteriophage therapy has emerged as a promising strategy due to its specificity to target bacteria, ability to penetrate and disrupt biofilms, and activity against multidrug-resistant organisms, while generally demonstrating a favorable safety profile with minimal effects on host tissues. This review critically evaluates current evidence for phage therapy in DFIs, which is dominated by in vitro studies, animal models, and a limited number of compassionate use and small clinical series. Reported outcomes show effectiveness against key pathogens including Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Enterococcus species, with preliminary evidence of reduced bacterial burden and improved wound healing in select patients. Despite these encouraging findings, clinical translation is challenged by narrow phage host ranges, the need for rapid phage-pathogen matching, standardization of production, regulatory hurdles, and incomplete understanding of pharmacokinetics and host immune interactions. Therefore, while phage therapy represents a potentially safe and effective adjunct to conventional DFI management, further well-designed preclinical studies and randomized clinical trials, alongside optimized delivery systems and regulatory frameworks, are required to fully establish its clinical utility.

Keywords:  antibiotics; diabetic foot infections; phage therapy

DOI:  https://doi.org/10.2147/IDR.S577526
J Wound Care. 2026 Apr 02. 35(4): 320-325

Micrografts-a novel ally in hard-to-heal wounds: a systematic review.

Gianmarco Polverino, Francesca Russo, Mariagiovanna Lombardi, Stefano Formica, Francesco D'Andrea.

   OBJECTIVE: Wound healing is complex, and hard-to-heal (chronic) wounds pose significant treatment challenges, especially in adults. Micrografts (MGs) are emerging as a promising treatment for wounds refractory to conventional approaches. MG involves transplanting a stem cell suspension to the wound to promote healing. Scientific studies on MG are increasing; however, a systematic review is needed for a comprehensive understanding of its efficacy.
METHOD: A systematic review conducted on 30 March 2024 used PubMed, Scopus and Web of Science databases to evaluate skin and dermal MGs in wound healing. PRISMA guidelines were followed and predefined inclusion and exclusion criteria were applied. All authors reviewed the studies and discussed results to ensure consistency in study screening, selection and data extraction.
RESULTS: A total of 1251 papers were examined, with 23 eligible for full-text review. After exclusions based on language, reviews, MG size and tissue focus, 15 articles were included in the final review: seven case reports; five case series; two prospective series (one with 70 patients, the other with 30 patients) and a case-control study.
CONCLUSION: The results of the reviewed studies suggest that MGs may promote wound healing, with reported reductions in healing time and improvements in clinical symptoms in hard-to-heal wounds. However, standardisation of treatment protocols and application methods is required. The role of MGs in the treatment of acute wounds remains to be clarified.

Keywords:  chronic wound; graft; hard-to-heal wound; micrograft; plastic surgery; stem cells; wound; wound care; wound dressing; wound healing

DOI:  https://doi.org/10.12968/jowc.2024.0145
J Wound Care. 2026 Apr 02. 35(4): 332-341

Bacterial composition and healing tendency with cold atmospheric plasma treatment in diabetic wounds.

Sybille Hasse, Liane Kantz, Jörn Schmidt, Thomas von Woedtke.

  Hard-to-heal (chronic) wounds in patients with diabetes represent a considerable, difficult-to-manage burden, and significantly increase the risk of amputations of lower extremities. These lesions are often accompanied by infections. Novel therapeutic approaches are urgently needed in the field of wound management. Cold atmospheric plasma (CAP) is a promising tool in the management of hard-to-heal wounds. Its beneficial use can be attributed to the reduction of bacterial load and direct stimulation of tissue regeneration. The effectiveness of different CAP devices for the treatment of hard-to-heal wounds is well documented by clinical case series and randomised controlled studies. The aim of this prospective, observational study was to investigate the bacterial load and composition in hard-to-heal wounds following CAP treatment, and the impact on long-term wound healing outcome. A total of 22 patients were included in the study. All wounds were exposed to the argon-driven CAP jet kINPen Med (neoplas med GmbH, Germany), in addition to standard phase-adapted wound care. A digital wound camera monitored wound area development over time, while swab tests monitored bacterial colonisation. The results showed that CAP application significantly reduced the bacterial burden almost immediately, although this reduction was not maintained. The analysis revealed a better healing tendency when wounds were colonised by Gram-positive bacteria as opposed to Gram-negative bacteria. Moreover, a higher susceptibility of Gram-negative bacteria to the CAP jet was detected. In conclusion, the bacterial composition of wounds might affect the healing outcome during CAP therapy.

Keywords:  CAP therapy; chronic wounds; cold atmospheric plasma; diabetes; hard-to-heal wounds; plasma jet; plasma medicine; wound; wound care; wound dressing; wound healing

DOI:  https://doi.org/10.12968/jowc.2023.0295
mBio. 2026 Mar 30. e0024326

The repertoire of resistance mutations selected by a Pseudomonas aeruginosa type IV pilus-targeting lytic bacteriophage.

Veronica N Tran, Hanjeong Harvey, Tanisha S Lahane, Lori L Burrows.

  Pseudomonas aeruginosa type IV pili (T4P) are complex surface-exposed nanomachines used for twitching motility and biofilm formation. Exposure to bacteriophages that use T4P as their primary receptor can select for resistance mutations that reduce or abolish pilus expression. Since T4P are important virulence factors, such loss can affect pathogenicity and fitness, which are desirable outcomes for phage therapy. Here, we evaluated the repertoire of mutations in P. aeruginosa PAO1 exposed to the pilus-specific lytic phage PO4 and their ability to revert after the removal of the phage. Resistant isolates ranged from hyperpiliated to bald, but none retained twitching motility. We focused on isolates that still expressed surface pili, including one with an internal four-amino acid duplication in the essential prepilin peptidase/methyltransferase, PilD. This duplication, distal to the predicted active sites, delayed prepilin processing. Accumulation of unprocessed subunits suppressed the expression of new prepilins via inhibition of PilSR two-component system activity, restricting the availability of functional subunits and conferring phage resistance. Introduction of a PilS point mutation that makes cells insensitive to the accumulation of unprocessed pilins restored motility and phage susceptibility. Of the mutants tested, only those with a duplication in pilD recovered wild-type motility following the removal of phage pressure, likely through slip-strand mispairing as a codon-modified variant did not revert. This work shows that resistance to pilus-specific phages does not require loss of pilus expression, and certain mutations can allow bacteria to regain pilus function. Characterizing spontaneous mutations selected by phages can help to define the function and vulnerabilities of the type IV pilus system.
IMPORTANCE: As the use of phages to treat antibiotic-resistant pathogens such as Pseudomonas aeruginosa increases, it is important to understand the potential outcomes of phage exposure. Most therapeutic P. aeruginosa phages use lipopolysaccharides or type IV pili (T4P) as primary receptors. Studying the properties of strains resistant to T4P-targeting phages can guide the design of phage cocktails to mitigate treatment resistance. We show that depending on the mutation, some phage-resistant strains can revert to wild-type sequences, emphasizing the importance of combining diverse phages to suppress resurgence. By characterizing mutations that confer resistance, we can better understand whether pilus structural or regulatory components are more likely to be lost. Using phages to select for the loss of pilus function represents an unbiased approach to identify new mutations in pilus-related proteins, shedding light on understudied components. Building a database of such mutations will help guide strategies to target and disarm this key P. aeruginosa virulence factor.

Keywords:  Pseudomonas aeruginosa; antibiotic resistance; bacteriophage therapy; bacteriophages; type II secretion; type IV pili

DOI:  https://doi.org/10.1128/mbio.00243-26
ISME J. 2026 Mar 28. pii: wrag067. [Epub ahead of print]

Rapid resistance evolution against phage cocktails.

Baltus A van der Steen, Matti Gralka, Yuval Mulla.

When bacteria are treated with multiple antibiotics simultaneously, resistance is highly unlikely to evolve. In contrast, resistance against multiple phages frequently arises during therapy. Why does resistance against multi-phage cocktails evolve so easily? Using a mathematical model, we show how the bacterial evolutionary dynamics and phage replicative dynamics uniquely intertwine, facilitating the rapid evolution of multi-phage resistance. As different phages replicate and become inhibitory at varying time points, bacteria can sequentially acquire resistance rather than simultaneously - increasing the chance of multi-resistance by orders of magnitude. We predict and experimentally verify a regime where multi-phage resistance is robustly prevented. Our findings provide a framework for the rational design of phage cocktails to curtail resistance development. Resistance can be minimized by reducing the dose of the most potent phages or by using phages with longer latent periods, as this helps synchronize multi-phage selection.

DOI: https://doi.org/10.1093/ismejo/wrag067
Front Pediatr. 2026 ;14 1770578

The neonatal lung microbiome: a dynamic determinant of respiratory health, disease, and novel therapeutics.

Wanwei Zheng, Yan Liang, Jiayao Li.

  The neonatal lung, once considered sterile, is now recognized to harbor a dynamic and complex microbiome that plays a critical role in respiratory health and disease. This review synthesizes current evidence on the composition, development, and functional impact of the lung microbiome in neonates, with a focus on its involvement in key respiratory disorders such as bronchopulmonary dysplasia, respiratory syncytial virus infection, neonatal acute respiratory distress syndrome, cystic fibrosis, and asthma predisposition. We place particular emphasis on the bidirectional communication along the gut-lung axis as a central mechanism, wherein intestinal microbiota and their metabolites modulate pulmonary immunity and inflammation. Emerging multi-omics studies that integrate microbial data with host metabolomic and immune profiles are highlighted for their role in deciphering disease-specific dysbiotic signatures and mechanistic pathways. Critically, this review advances the discussion beyond association by evaluating the translational potential of the microbiome as both a diagnostic biomarker and a therapeutic target. We provide a critical appraisal of innovative microbiome-targeted strategies-including probiotics, postbiotics, phage therapy, and bacterial lysates-and discuss the unique challenges and future directions for translating these approaches into safe, effective clinical interventions for vulnerable neonates. By bridging foundational science with clinical implications, this work aims to inform the development of novel, ecology-informed therapeutics to prevent and mitigate neonatal respiratory diseases.

Keywords:  dysbiosis; lung microbiome; microbiome therapeutics; neonatal respiratory disorders; probiotics; short-chain fatty acids

DOI:  https://doi.org/10.3389/fped.2026.1770578
Front Cell Infect Microbiol. 2026 ;16 1779296

Phage characterization analysis in respiratory samples from infected patients based on metagenomic next-generation sequencing.

Yuyan Huang, Qingqing Cai, Yingying Chen, Direerba Amutijiang, Yihan Lu, Weifeng Huang, Ling Li.

   Background: Respiratory tract infections are common infectious diseases, with microbial dysbiosis closely linked to clinical outcomes in the host. As key regulators of bacteria, phages can influence the structure and stability of microbial communities by infecting host bacteria. Metagenomic next-generation sequencing (mNGS) enables comprehensive analysis of phage community characteristics in clinical samples.
Methods: This study included 6,404 clinical samples, comprising 4,837 bronchoalveolar lavage fluids (BALF) and 1,567 sputum samples, for metagenomic next-generation sequencing (mNGS), while collecting patient demographics, sample types, mNGS results, and clinical outcomes. Host-derived sequences were removed post-sequencing and aligned against viral reference databases. Phage community structures across sample types were assessed using alpha and beta diversity metrics. Spearman correlation analysis explored associations between phages and bacteria. Further bioinformatics analysis was performed on 194 samples, including viral sequence assembly and identification using SPAdes, VirSorter2, and PhaMer; CD-HIT clustering and redundancy removal; CheckV quality assessment; PhaTYP lifestyle prediction; Prodigal protein gene annotation; and BLASTP alignment against the CARD database to screen for phage resistance genes.
Results: The sputum and BALF groups exhibited comparable richness, diversity, and evenness, yet their community structures differed significantly. Intensive Care Unit (ICU) admission status was closely associated with reduced phage community diversity and significant alterations in community structure, and the abundance distribution of several phage families (Peduoviridae, Autoscriptoviridae, Casjensviridae, Demerecviridae) also changed significantly. Additionally, the phage community structure in sputum samples was significantly associated with patient clinical outcomes. Correlation analysis demonstrated that the Aliceevansviridae family in sputum samples had extensive positive associations with various bacteria. After assembly, 69.5% of pOTUs were predicted to be temperate phages, and 28.9% were predicted to be virulent phages; moreover, the vast majority (99.2%) of phage sequences showed low similarity to antibiotic resistance genes.
Conclusion: This study identifies distinct phage community characteristics across respiratory sample types and reveals that ICU patients exhibit reduced phage diversity and markedly altered community structures. Furthermore, the phage composition in upper respiratory tract samples shows a clear relationship with patient prognosis, providing new insights into respiratory infection microecology.

Keywords:  bronchoalveolar lavage fluid; metagenomic next-generation sequencing (mNGS); phage; respiratory tract infection; sputum

DOI:  https://doi.org/10.3389/fcimb.2026.1779296
Gut Microbes Rep. 2025 ;2(1): 2452485

Characterization of an Indigenous Lytic Phage Targeting Multidrug-Resistant Salmonella enterica.

Ebele Onuigbo, Paul Akpa, Anthony Attama, Stephen Emencheta, Emmanuel Eze, Chinonye Obeta.

  Multidrug-resistant pathogens have prompted the use of lytic bacteriophages. An indigenous novel lytic bacteriophage against Salmonella enterica strains from environmental wastewater was isolated and characterized using phage survivability study, adsorption curve, one-step curve, optimal multiplicity of infection, and phage-killing assay. The Salmonella strains CP90 and CP23 isolated from the same source were biochemically and molecularly characterized. The Salmonella strains CP90 and CP23 had 96.24% and 97.18% pairwise identity respectively with S. enterica. Both were resistant to B-lactam Aminoglycosides, Penicillin, and Phenicol class of antibiotics. The phage performed better in an alkaline medium and below 50°C. About 80% of the phage had an adsorption rate of 12 min and a latent period of 20 min. About 55 PFU/cell of the phage was released during a single replication cycle, inhibiting bacteria growth for up to 5 h. The characterization of this indigenous phage suggests its therapeutic potential against multidrug-resistant Salmonella species.

Keywords:  Bacteriophage; Salmonella enterica; lytic; native; therapy

DOI:  https://doi.org/10.1080/29933935.2025.2452485
Mol Biol Rep. 2026 Mar 31. pii: 561. [Epub ahead of print]53(1):

Metagenome-based insights into bacteriophage diversity of an urban river ecosystem.

Abhiruchi Varshney, Indira P Sarethy.



Keywords:  Antimicrobial resistance; Bacteriophages; ESKAPE Pathogens; Metagenomics; Yamuna River

DOI:  https://doi.org/10.1007/s11033-026-11731-z
Gut Microbes. 2026 Dec 31. 18(1): 2653288

Neglected kingdoms: the gut virome, mycobiome and their role in inflammatory bowel disease.

Yashar Houshyar, Fan Zhang, Paris Tavakoli, Michael C Grimm, Georgina L Hold.

  Inflammatory bowel disease (IBD) is a chronic relapsing-remitting disorder of the gastrointestinal tract characterized by immune dysregulation, epithelial barrier dysfunction, and microbial imbalance. While bacterial dysbiosis, including depletion of short-chain fatty acid (SCFA) producers and enrichment of pathobionts, is well characterized, the gut virome and mycobiome remain comparatively neglected. Both exhibit high variability and are constrained by sequencing bias, contamination, and incomplete reference databases, leaving much of the viral and fungal diversity unresolved. Emerging evidence links fungal and viral dysbiosis to IBD pathogenesis, including Candida overgrowth, loss of Saccharomyces, expansion of Caudoviricetes phages, and detection of eukaryotic viruses such as Cytomegalovirus and Epstein-Barr virus in inflamed mucosa. These alterations disrupt barrier integrity, modulate immune signaling, and interact with bacteria and archaea in cross-kingdom networks that amplify inflammation. Translationally, the virome and mycobiome are now recognized as therapeutic targets, inspiring interventions from pre/probiotics and synbiotics to precision phage therapy and microbiota-based transplantation, including fecal virome transplantation (FVT) and fecal microbiota transplantation (FMT). This review recognizes the challenges and opportunities of studying these neglected kingdoms, reframes IBD dysbiosis and highlights new directions for biomarker discovery and multikingdom microbiota-directed therapies.

Keywords:  Crohn's disease; Inflammatory bowel disease; microbiome; mycobiome; ulcerative colitis; virome

DOI:  https://doi.org/10.1080/19490976.2026.2653288
IEEE J Biomed Health Inform. 2026 Mar 31. PP

Semantic fusion of dual perspectives on genomic sequences and quorum sensing for bacteriophage lifestyle prediction.

Zhen Xiao, Ankang Wei, Yi Jia, Weizhong Zhao, Xingpeng Jiang.

As the most ubiquitous and abundant viral community, bacteriophages (phages for short) play a vital role in regulating the ecological balance by infecting bacteria and archaea. Phages can be classified into two types based on their lifestyles: virulent phages and temperate phages, which are closely related to their functional characteristics and influence their interaction patterns with hosts. Therefore, identifying phage lifestyle is critical for understanding the mechanisms by which phages infect bacteria and represents a key step in mastering their functions and potential applications. In this paper, we propose a novel method for phage lifestyle identification by considering two perspectives. One perspective is based on the genomic sequences of phages, in which both local and global semantic features are integrated. The other perspective focuses on the host quorum sensing phenomena that influence phage lysogen-lysis decisions. Specifically, we first capture local sequence variation patterns by extracting the relative positional information of nucleotide fragments at different intervals, which enables robust representation of local genomic semantics. Secondly, the pretrained nucleotide language model DNABERT is applied to capture the semantics of genome sequences by considering the global contextual information. Finally, combined with quorum sensing signals from the bacterial host, a final fusion representation is obtained, which is fed into a predictive model to identify the phage's lifestyle. Experimental results show that our method has excellent and stable performance in both phage complete genome and short contigs from metagenomic data. We also investigate early-life viral colonization in the human gut metagenome, further validating the model's generalizability and real-world applicability.

DOI: https://doi.org/10.1109/JBHI.2026.3679001
PLoS Biol. 2026 Mar 31. 24(3): e3003737

Biofilm spatial structure and superinfection immunity modulate inter-phage competition.

James B Winans, Carey D Nadell.

Obligately lytic (virulent) phages always lyse host cells to release progeny viruses, while temperate phages can either lyse their hosts or integrate into host genomes as prophages, forming lysogens. There is a rich history of work studying the relative advantages and disadvantages of these two phage life history strategies, but little of this work has addressed the spatial constraints common to biofilm environments. We developed a live imaging system to track lytic infections, lysogenic infections, and uninfected cells at single-cell resolution within three-dimensional Escherichia coli biofilms. We find that biofilm structure substantially impacts the ecological success of different phage infection strategies. Temperate phages have the unique capacity to release phages from lysogens that have undergone lytic induction from within the interior of mature biofilms. When this occurs in biofilm contexts that do not limit phage diffusion, lytic infections expand rapidly, but lysogenic infections are favored as phage mobility declines in densely packed biofilm architectures. In matrix-replete biofilms that do limit phage mobility, lytic phage infection is more limited, favoring lysogenic growth. Direct competition assays between lysogenized host bacteria and obligately lytic phages-with or without the ability to superinfect lysogens-revealed that spatial structure and superinfection potential together greatly impact phage competition outcomes during co-invasion into pre-existing, phage-susceptible biofilm populations. Highly packed, phage diffusion-impeding biofilms disproportionately favored temperate phages in the lysogenic cycle over obligate lytic phages, highlighting how biofilm architecture can constrain lytic phage infection and promote vertical phage genome transmission strategies.

DOI: https://doi.org/10.1371/journal.pbio.3003737
JMIR Nurs. 2026 Mar 30. 9 e85644

Artificial Intelligence-Enhanced Wound Care to Improve Access, Efficacy, and Equity in Wound Care for Older Adults in Rural and Remote Regions of Canada.

Courtney Genge, Basnama Ayaz, Shannon Freeman, Heba Tallah Mohammed, Robert D J Fraser, Ibukun-Oluwa Omolade Abejirinde, Deirdre O'Sullivan-Drombolis, Rebecca Brookham.

   Unlabelled: Wound care is an increasing global challenge, with older adults among those most affected. As populations age, the demand for effective and efficient wound care increases. Over the years, various wound assessment and care techniques have been developed, including digital wound care technology (DWCT), which uses innovative artificial intelligence (AI). Many older adults, especially those living in rural and remote areas, face significant barriers in obtaining timely and effective wound care, leading to poorer health outcomes and increased health care costs related to wound care. These challenges underscore the urgent need to implement wound care models that equitably improve access to care and enhance clinical outcomes, particularly for older adults, to promote healthy aging and age-in-place. Based on evidence from the literature and the initial implementation of a DWCT in 2 community health systems in Ontario, this viewpoint paper encourages clinicians and health care leaders to embrace and expand the implementation of an AI-driven DWCT to address inequities in access to high-quality, timely care. The experiences from these implementations indicate that the use of AI can support clinical decision-making and extend access to care for individuals in rural and remote communities in Canada. By leveraging DWCT powered by AI, health care providers can enhance the accuracy and consistency of wound assessments, improve communication, streamline care processes, and more effectively allocate resources, ultimately aiming to reduce disparities in wound care outcomes. .

Keywords:  AI; artificial intelligence; equity; wound care

DOI:  https://doi.org/10.2196/85644
Infect Disord Drug Targets. 2026 Mar 31.

A Review on Models for Wound Healing.

Deepshikha Dubey, Yogesh Murti, Akash Ved, Sachdev Yadav, Karuna Shanker Shukla, Mayank Kulshreshtha.

  Developing efficient therapies for both acute and chronic wounds requires a thorough un-derstanding of wound healing mechanisms and possible therapeutic approaches. Preclinical research simulates wound healing processes and evaluates the effectiveness of novel medications and treat-ments using a range of experimental models. This review examines and contrasts the main preclinical models-in vitro, in vivo, in silico, explant, and genetically modified models that are employed in wound healing research. While in vivo models offer insights into complex tissue connections and systemic effects in animal subjects, in vitro models facilitate specific cellular and molecular studies to be conducted under controlled settings. The use of in silico models can reduce the requirement for animal testing by supporting predictive analysis and the computational simulation of wound healing processes. Explant models, which bridge the gap between cell cultures and whole-animal models, provide a more complicated environment than in vitro methods by using portions of tissue or organs. Furthermore, targeted research on gene-specific involvement in wound healing is enabled by genet-ically modified models, which are frequently based on animals with particular gene changes. These models' relative advantages and disadvantages are examined, emphasizing their applicability and complementary functions in experimental wound repair studies. This thorough analysis provides a cohesive perspective on each model's suitability, which aids in the development of preclinical ap-proaches for wound healing treatments.

Keywords:  Screening; explants.; in vitro; in vivo; models; wound healing

DOI:  https://doi.org/10.2174/0118715265408774251110041638
J Cyst Fibros. 2026 Mar 31. pii: S1569-1993(26)00093-7. [Epub ahead of print]

Changes in nutritional priorities and management in people with CF.

Jessica A Alvarez, Sarah Jane Schwarzenberg, Nicole Green.

  Nutritional priorities for people with cystic fibrosis (PwCF) are shifting rapidly with widespread use of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators. As undernutrition becomes less common with increasing longevity, adiposity- and age-driven metabolic risks have emerged as growing concerns for the CF population. Evidence now demonstrates that lean mass and muscle function, rather than body weight alone, are more closely aligned with pulmonary health, although these relationships may be altered based on CFTR modulator use. Modern nutrition care guidelines emphasize individualized assessment, body composition monitoring, optimization of diet quality, and lifestyle strategies that support muscle health and metabolic resilience. Additionally, growing understanding of gut dysbiosis and its potential modulation through diet, probiotics, and CFTR modulator therapy highlights new opportunities to improve gastrointestinal and systemic health. Together, these evolving insights underscore the need to modernize nutrition targets and develop evidence-based dietary and behavioral interventions suited to an aging CF population in the modulator era.

Keywords:  Body composition; CFTR modulator; Cystic fibrosis; Diet; Gastrointestinal dysbiosis; Nutrition

DOI:  https://doi.org/10.1016/j.jcf.2026.03.026
Talanta. 2026 Mar 31. pii: S0039-9140(26)00408-X. [Epub ahead of print]306 129752

Multifunctional nanozyme systems for combating bacterial infections in wound treatment.

Olga I Guliy, Lev A Dykman.

  Bacterial penetration of the wound surface results in acute and chronic infections and in delayed wound healing. Patients' quality of life declines, and healthcare systems throughout the world are under increased stress. Novel artificial enzymes called nanozymes are capable of controlling the wound microenvironment and effectively mimicking the activity of natural enzymes. They have the advantages of being very steady and affordable. They speed up the healing of infected wounds, restore blood vessels, and reduce oxidative stress and blood glucose levels. Nanozyme-based therapy is a potentially successful wound-treatment strategy when combined with other components. This article reviews important data on the development of chronic wounds and on the potential of nanozyme technology for their treatment. It provides new insights into the rapidly growing field and will help researchers to choose nanozyme design strategies depending on the desired therapeutic outcome in wound healing. Finally, it examines methods for enhancing the current nanozyme-based treatment techniques and provides an overview of the most recent developments in nanozyme-based wound therapy.

Keywords:  Enzymes; Nanomaterials; Nanozymes; Wound treatment

DOI:  https://doi.org/10.1016/j.talanta.2026.129752
Zhonghua Kou Qiang Yi Xue Za Zhi. 2026 Mar 31. 61(4): 582-588

[From oral microbiome dysbiosis to renal injury: research advances in the mechanism of association between periodontitis and diabetic kidney disease].

X Y Wang, Y J Yao, L L Li, F H Yan.

Periodontitis, a chronic inflammatory disease driven by dysbiosis of the oral microbiome, has increasingly been recognized for its systemic impact beyond the oral cavity. Growing evidence links periodontitis to the onset and progression of diabetic kidney disease (DKD), suggesting that disturbances of oral microbial homeostasis may influence distant organs through systemic circulation or the oral-gut-kidney axis. Such interactions can trigger systemic inflammation, immune dysregulation, oxidative stress, and metabolic disturbances, thereby accelerating renal injury. This review summarizes recent advances on the potential mechanisms linking periodontitis to DKD progression and highlights the key role of oral microbial dysbiosis and related systemic effects.

DOI: https://doi.org/10.3760/cma.j.cn112144-20251112-00446
Front Microbiol. 2026 ;17 1778984

Bacteriophages targeting Acinetobacter baumannii in the era of antibiotic failure: a review.

Jamil Allen G Fortaleza, Kevin Smith P Cabuhat, Shukho Kim, Ferdinand A Mortel, Grace D Bacalzo, Jose Jurel M Nuevo.

  Acinetobacter baumannii has become a prominent healthcare-associated pathogen due to its exceptional environmental persistence, biofilm-forming capacity, and the global emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant lineages. The declining effectiveness of conventional antibiotics has renewed interest in bacteriophage-based strategies as alternative or adjunctive antimicrobial approaches. This review provides a comprehensive synthesis of recent advances in bacteriophages targeting A. baumannii, integrating microbiological, structural, immunological, and translational perspectives that shape therapeutic efficacy and resistance dynamics. We highlight the central role of bacterial surface structures, including capsular polysaccharides, outer membrane proteins, and lipooligosaccharides, which act simultaneously as virulence determinants, phage receptors, and modulators of antimicrobial susceptibility. Phage-mediated antibacterial activity is achieved through receptor-specific lysis, biofilm disruption, capsule and envelope remodeling, and indirect resensitization to antibiotics, frequently accompanied by fitness trade-offs in phage-resistant bacterial subpopulations. We further discuss how formulation strategies, phage-derived enzymes, engineered phages, and phage-antibiotic combinations influence treatment outcomes, with particular attention to delivery routes, dosing strategies, and host immune context. Importantly, we distinguish direct phage effects from secondary immunological consequences of bacterial clearance and critically evaluate evidence from in vitro studies, animal infection models, and emerging clinical reports. Finally, we examine regulatory and manufacturing challenges that currently limit broader clinical translation. This review positions bacteriophage-based interventions as a promising, evolution-aware complement to antibiotics for managing drug-resistant A. baumannii, while underscoring the requirements for their rational and durable clinical implementation.

Keywords:  biofilm; endolysin; engineered phage; multi-drug resistance; phage-antibiotic combination

DOI:  https://doi.org/10.3389/fmicb.2026.1778984
Nurse Educ Pract. 2026 Mar 18. pii: S1471-5953(26)00091-0. [Epub ahead of print]93 104789

Secure and accessible AI in nursing education: A modular agentic chatbot framework comparing ChatGPT-4o with an open-source LLM for chronic wound care.

Necip Gurler, Tuba Sengul, Samet Husnu Bulbul, Dilek Yilmaz Akyaz, Ozgur Guler, Asım Evren Yantac, Emir Bedirhan Aydın, Holly Kirkland-Kyhn.

   AIM: To develop and evaluate a modular agentic AI chatbot framework for chronic wound care education in nursing and to compare open-source and commercial configurations.
BACKGROUND: Integrating artificial intelligence (AI) into nursing education can enhance learning experiences, but widespread adoption is limited by costs, data governance and concerns about model reliability. Modular, retrieval-augmented generation (RAG)-based agentic AI frameworks might address these limitations by improving accuracy, flexibility and local control.
DESIGN: A comparative experimental pre-implementation study using a validated 100-item chronic wound care question dataset aligned with international clinical guidelines.
METHODS: A modular, agentic chatbot framework employing RAG technology was developed and evaluated using open-source and commercial AI models. Six experts independently rated responses on accuracy, relevance, clarity and coverage using a 5-point Likert scale. Analyses included linear mixed-effects modeling and Wilcoxon signed-rank tests. Dataset validity was confirmed using the Davis technique.
RESULTS: Both chatbot configurations produced clinically accurate, guideline-aligned responses. The commercial model achieved higher overall scores (mean difference = +1.01 on a 20-point scale, p < 0.001), with the largest domain-specific difference observed in coverage (+0.39 on a 5-point scale, p < 0.001). The open-source configuration demonstrated strong adherence to guidelines, with 56% of responses fully aligned with clinical recommendations.
CONCLUSIONS: The open-source, on-premises AI agent demonstrated near-comparable performance to ChatGPT-4o while offering clear advantages in cost, security and institutional autonomy. Its capacity to support guideline-based instruction and promote equitable access makes it a promising tool for nursing education.

Keywords:  Artificial intelligence: AI agent; Chatbot; Chronic wound management; Nursing education; On-premises framework; Open-source AI; Retrieval-augmented generation (RAG)

DOI:  https://doi.org/10.1016/j.nepr.2026.104789
Drug Dev Res. 2026 Apr;87(2): e70270

Blueprint for Drug Repurposing Success: Foundational Concepts and Practical Framework.

Aayusree Ray, Shreya Dey, Debjeet Sur.

  Drug repurposing involves identifying new therapeutic applications for existing clinically evaluated compounds. In contrast to conventional drug development, which typically spans over a decade and demands substantial financial investment, repurposed drugs can achieve regulatory approval in approximately half the time and cost by capitalizing on their established pharmacokinetic, safety, and clinical profiles. This review provides a comprehensive analysis of the traditional and computational strategies employed in drug repurposing. Experimental methodologies include binding affinity assays, clinical data mining and phenotype-based screening. Computational approaches are categorized into structure-based, signature-based, pathway-based, knowledge-based, and target-based strategies. The recent integration of artificial intelligence (AI) and machine learning (ML) within repurposing pipelines is also examined, emphasizing their ability to efficiently process large-scale datasets, improve the predictive accuracy of drug-target interactions, and support the advancement of repurposing efforts. Furthermore, this review systematically compares prominent computational platforms, virtual screening tools, and bioinformatics resources, highlighting their respective strengths and limitations. Emerging AI-driven models, such as deep learning architectures, graph neural networks, knowledge graphs, and network pharmacology frameworks, have transformative roles in broadening the scope of drug repurposing. This comprehensive review is intended to assist medicinal chemists, computational biologists, and drug discovery scientists in expediting research efforts by effectively utilizing existing resources for repurposing-driven innovations.

Keywords:  artificial intelligence; computational drug discovery; drug discovery; drug repurposing; translational research

DOI:  https://doi.org/10.1002/ddr.70270
Int Forum Allergy Rhinol. 2026 Mar 31.

Biofilm Exoproteins From Staphylococcus Species Impede Re-Epithelialization of Nasal Epithelial Cells During Wound Healing and Cease Ciliary Beat Frequency.

Sintayehu Ambachew, Mahnaz Ramezanpour, Clare M Cooksley, Emma F Barry, Lindsay Durr, Kevin Aaron Fenix, P J Wormald, Alkis J Psaltis, Sarah Vreugde.

   INTRODUCTION: Chronic rhinosinusitis (CRS) is an inflammatory disease with many different contributing factors, including bacterial infection. CRS patients are typically managed with medical therapies; however, these treatments frequently fail, leaving surgery as the only viable option. Despite surgical intervention, patients may experience ongoing clinical manifestations of inflammation and infection, frequently associated with Staphylococcus species colonization. This study explored the influence of Staphylococcus on the wound healing process and ciliary function in vitro.
METHODS: Exoproteins were extracted from biofilm forms of 15 Staphylococcus isolates obtained from five patients (4 CRS and 1 control patient), each colonized by Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus lugdunensis. Human nasal epithelial cells (HNECs) were cultured in monolayers for wound healing assays and at an air-liquid interface (ALI) for ciliary beat frequency measurements. Wound closure, cytotoxicity, interleukin-6 (IL-6), and reactive oxygen species (ROS) release were measured after 30 h post-wound creation.
RESULTS: Biofilm exoproteins from all three Staphylococcus species hindered the re-epithelialization of HNECs at 5 and 10 µg/mL with S. aureus exoproteins having significantly stronger effects on impairing wound closure compared to S. lugdunensis exoproteins. S. aureus exerted the most pronounced cytotoxic effect compared to the control. Furthermore, all Staphylococcus species reduced ROS release by HNECs while S. epidermidis and S. lugdunensis induced higher IL-6 levels compared to control. In HNEC-ALI cultures, ciliary beat frequency was significantly reduced by all staphylococci 5 h after application of exoproteins.
CONCLUSION: Staphylococcal biofilm exoproteins hindered mucociliary function and re-epithelialization of the nasal epithelium, caused cytotoxicity, elicited inflammation, and concurrently reduced ROS release.

Keywords:  biofilm exoproteins; ciliary beat frequency; cytotoxicity; inflammation; nasal epithelium; staphylococci; wound healing assay

DOI:  https://doi.org/10.1002/alr.70146
Microb Pathog. 2026 Mar 26. pii: S0882-4010(26)00193-2. [Epub ahead of print]215 108467

Dismantling S. aureus virulence: Latest advances in toxin neutralization and regulatory network-targeted anti-virulence strategies (2025).

Wenwen Jiang, Chongge You.

  Staphylococcus aureus remains a leading cause of severe bacterial infections worldwide, exacerbated by rising antibiotic resistance, particularly in methicillin-resistant strains (MRSA), and the pathogen's ability to form persistent biofilms and evade host immunity through sophisticated virulence mechanisms. Conventional antibiotic therapies often fail against chronic, recurrent, and invasive infections due to resistance emergence, inadequate penetration into biofilms, and inability to neutralize toxin-mediated tissue damage.Anti-virulence strategies, which disarm pathogens without exerting direct bactericidal pressure, have emerged as promising adjunctive or alternative approaches. This review synthesizes the most recent advances (up to early 2026) in dismantling S. aureus virulence, focusing on toxin neutralization and regulatory network-targeted interventions. Key strategies include toxin-neutralizing monoclonal antibodies (suvratoxumab, tosatoxumab, and the discontinued ASN100 combination), SaeR inhibitors (e.g., HR3744, SAV13), RNAIII-blocking peptides, nanoparticle-based "decoy" systems, natural compounds modulating quorum sensing and toxin expression, and multivalent toxoid vaccines (notably LBT-SA7, which received FDA Fast Track designation in late 2024 and initiated Phase 1 trials in 2025 for the prevention of skin and soft tissue infections). Preclinical and early clinical data demonstrate that toxin neutralization reduces disease severity and enhances antibiotic efficacy in animal models and select patient cohorts, though several monoclonal antibodies have faced challenges in achieving primary endpoints in larger trials. Major translational hurdles persist, including virulence factor redundancy, extensive strain heterogeneity, suboptimal pharmacokinetics, and potential for compensatory adaptations. Nevertheless, synergistic combinations with conventional antibiotics and precision-guided, multi-target regimens informed by individual virulence profiling hold substantial promise for improving outcomes in chronic, resistant, and biofilm-associated S. aureus infections.

Keywords:  Anti-virulence; Monoclonal antibodies; Precision therapy; Regulatory inhibitors; Staphylococcus aureus; Toxin neutralization; Toxoid vaccines

DOI:  https://doi.org/10.1016/j.micpath.2026.108467
NPJ Biofilms Microbiomes. 2026 Apr 03.

Deep learning-based high-information-content graph representation of early stage bacterial biofilms.

Lev E Nersesyan, Daniil A Boiko, Saniyat Kurbanalieva, Lilya U Dzhemileva, Konstantin S Kozlov, Valentine P Ananikov.

Bacterial biofilms are complex, spatially organized microbial communities that exhibit enhanced resistance to antibiotics and contribute to chronic infections. Understanding their structure, especially during early formation stages, is critical for developing effective intervention strategies. Here, we present a high-resolution computational framework that models biofilms as undirected interaction graphs, where individual bacterial cells are vertices and predicted intercellular interactions are edges. Combining microscopy visualization and deep learning, we developed a pipeline that integrates Mask R-CNN for cell segmentation and a custom neural network (BINet) for interaction prediction. The described graph-based representation enables quantitative analysis of biofilm growth, identification of recurrent structural motifs, and classification of substrate-specific colonization patterns. We demonstrate the utility of this approach in predicting both the developmental stage and material type from image-derived graph features. This study provides the tool for revealing nonobvious patterns of biofilm organization and describes a scalable, high-information-content approach for the automated analysis of microbial communities, opening new possibilities for systems-level microbiological research.

DOI: https://doi.org/10.1038/s41522-026-00971-3
Endocr Pract. 2026 Apr 01. pii: S1530-891X(26)00930-4. [Epub ahead of print]

Puberty and Growth in Cystic Fibrosis: A Review.

Nellie Hani, Marissa Kilberg, Sara Bartz, Andrea Kelly.

  Cystic fibrosis (CF) is a chronic disease process that has historically been associated with delayed puberty and growth. Mechanisms for delayed growth and puberty in chronic disease include malnutrition, inflammation, alterations of the growth hormone axis, chronic corticosteroid use, and changes to gonadotropin signaling or release. Early evidence suggested that people with CF (pwCF) have delayed puberty, decreased peak height velocity, and decreased final adult height compared to the general population. Management of delayed puberty in CF typically involves addressing the underlying cause of delay, and evidence for the utility of growth hormone to optimize growth in pwCF is inconsistent. In the era of highly effective modulator therapies (HEMT) for CF, early studies are examining changes in the growth and puberty trajectory in youth with CF. The full impact of HEMT on height outcomes remains unclear.

Keywords:  Chronic illness; Cystic Fibrosis; Growth; Highly Effective Modulator Therapy; Puberty

DOI:  https://doi.org/10.1016/j.eprac.2026.03.105
J Vasc Bras. 2026 ;25 e20250097

Systemic antibiotics for diabetes mellitus-related foot infections: an integrative literature review.

Catarina França Dos Santos, Vanessa Prado Dos Santos, Lucas de Mello Ferreira, Neima Prado Dos Santos, André Brito Queiroz, Valter Castelli, Roberto Augusto Caffaro, Carlos Alberto Silveira Alves.

  Evidence on antibiotic therapy for diabetic foot infections can help clinical management. The objective of this study was to identify the evidence on systemic antibiotics for treatment of diabetes mellitus-related foot infections. An integrative literature review was conducted of randomized clinical trials, systematic reviews, and meta-analyses. The keywords "Diabetic foot" AND "Antibiotics" were used to search PubMed and 15 articles were selected (nine randomized clinical trials, four systematic reviews, and two meta-analyses). Seven randomized clinical trials revealed clinical results that were comparable for beta lactam antibiotics with beta-lactamase inhibitors, carbapenems, and fluoroquinolones. Two randomized clinical trials found significant differences comparing ertapenem and tigecycline and in analyses of subsets with severe infections between piperacillin-tazobactam and ertapenem. The literature revealed comparable clinical results for different systemic antibiotics used to treat foot infections related to diabetes, except for the difference between ertapenem and tigecycline, which did not meet the parameters for non-inferiority, highlighting the need for higher-quality evidence.

Keywords:  antibiotics; diabetes mellitus; diabetic foot; infection; treatment

DOI:  https://doi.org/10.1590/1677-5449.202500972
Int J Nanomedicine. 2026 ;21 572181

Antimicrobial Hydrogel for Diabetic Wound Treatment.

Huan Huang, Puhua Zhang, Songjie Li, Qiuhe Song, Zhongcheng Hu, Chunxia Zhou, Lei Yang.

  Diabetic wound infections pose a significant clinical challenge. Chronic wounds associated with diabetes mellitus exhibit delayed healing and, if not managed appropriately, are highly susceptible to infections that may lead to life-threatening complications in severe cases. Antimicrobial hydrogels have become promising materials for diabetic wound management due to their moisture retention, biocompatibility, biodegradability, and intrinsic antimicrobial properties. As wound dressings, they offer advantages such as wound exudate absorption, controlled drug 2release, and minimized toxic side effects. By incorporating antimicrobial components (e.g. chitosan (CS), polyethylenimine (PEI)) or serving as carriers for antimicrobial agents (e.g. antibiotics, antimicrobial peptides (AMPs), inorganic metal materials, and carbon nanomaterials (CNMs)), antimicrobial hydrogels effectively inhibit microbial growth. With ongoing research, the development of intelligent, multifunctional, and highly responsive antimicrobial hydrogels continues to advance, offering more precise and rapid therapeutic solutions for diabetic wounds. This review first examines the impact of infection on diabetic wound healing, followed by an overview of the definition and classification of hydrogels. Subsequently, various antimicrobial hydrogels and their mechanisms of action are summarized, along with an exploration of their fabrication methods. By analyzing recent advancements in antimicrobial hydrogel research, this review aims to provide insights into future research directions and potential clinical applications for diabetic wound management.

Keywords:  antimicrobial hydrogel; diabetic wound; hydrogel; wound healing

DOI:  https://doi.org/10.2147/IJN.S572181
J Microbiol. 2026 Mar;64(3): e2512002

Emerging synthetic biology-assisted technologies for overcoming antibiotic resistance: CRISPR-Cas, bacteriophage, microbiome, and metabolic engineering-based solutions.

Yujeong Oh, Hyunjin Lee, Sungho Jang.

  Antibiotic resistance has become a critical global health challenge due to the decreased efficacy of existing antibiotics and the emergence of multidrug-resistant pathogens. In particular, the rapid horizontal transfer of resistance genes and the diverse mechanisms by which bacteria acquire resistance have significantly undermined the effectiveness of conventional therapeutic strategies, revealing fundamental limitations in current infectious disease management. In this context, synthetic biology provides a promising framework to overcome the limitations of conventional antibiotics by integrating engineering principles with bioengineering approaches, thereby enabling precise and programmable control of biological processes. These synthetic biology-based approaches offer substantial potential for developing sustainable and highly specific antimicrobial strategies. This review comprehensively examines recent advances in synthetic biology-assisted antimicrobial strategies, including CRISPR-Cas systems, bacteriophage engineering, microbiome engineering, and metabolic engineering-driven antibiotic discovery. Collectively, these approaches represent a precision antimicrobial paradigm that enables selective targeting of resistant bacteria while preserving microbiome homeostasis. These strategies also provide new directions for limiting resistance dissemination and guiding the development of next-generation therapeutics.

Keywords:  CRISPR-Cas; antibiotic resistance; bacteriophage engineering; metabolic engineering; microbiome engineering; synthetic biology

DOI:  https://doi.org/10.71150/jm.2512002
Front Physiol. 2026 ;17 1776883

Clinical applications of machine learning for infection assessment in diabetic foot ulcers.

Khrystyna Lysnychka, Larysa Rostoka, Yana Burmistrova, Iryna Halabitska, Pavlo Petakh, Oleksandr Kamyshnyi.

  Diabetic foot ulcers (DFUs) represent one of the most severe complications of diabetes mellitus and are frequently complicated by infection, which significantly increases the risk of hospitalization, lower-limb amputation, and mortality. Early and accurate detection of infection in DFUs is therefore critical; however, clinical assessment remains challenging and is largely based on subjective visual evaluation. Inter-observer variability, atypical inflammatory responses in patients with diabetes, and inconsistent wound documentation contribute to delayed or inaccurate diagnoses. In recent years, digital sound imaging combined with machine learning (ML) techniques has emerged as a promising adjunct to traditional clinical assessment. This review summarizes and critically evaluates recent advances in the application of ML for infection assessment in DFUs. We review image-based ML approaches designed to detect infection-related visual features, including erythema, purulent exudate, necrosis, and tissue discoloration, as well as models developed for ulcer classification, tissue segmentation, and longitudinal wound monitoring. In addition, we discuss the clinical utility of ML-assisted tools in telemedicine, remote monitoring, and decision support, particularly in community and resource-limited settings. Current limitations, including image variability, dataset bias, lack of standardized imaging protocols, and limited clinical validation, are also addressed. Overall, ML-based systems have demonstrated encouraging performance in identifying infection-associated patterns in DFU images and may help reduce diagnostic variability and support earlier clinical intervention. Nevertheless, further large-scale prospective studies, regulatory validation, and integration into clinical workflows are required before widespread adoption. Machine learning should be viewed as a supportive tool that complements, rather than replaces, clinical expertise in the management of diabetic foot infections.

Keywords:  artificial intelligence; clinical decision support; diabetic foot infection; diabetic foot ulcer; digital wound imaging; machine learning; medical image analysis; telemedicine

DOI:  https://doi.org/10.3389/fphys.2026.1776883
Curr Opin Microbiol. 2026 Mar 28. pii: S1369-5274(26)00035-4. [Epub ahead of print]91 102741

Rise of the viral giants: common themes underlying genome gigantism in eukaryotic viruses and bacteriophages.

Sofia Rigou, Joud Aldaroub, Matthias Horn, Frank O Aylward.

Recent research has shown that the biosphere harbors an immense diversity of large and complex DNA viruses that infect a wide range of hosts. This is best exemplified by giant viruses of eukaryotes (phylum Nucleocytoviricota) and large phages, also referred to as jumbo phages, that infect bacteria (class Caudoviricetes). Both groups independently evolved large genomes and complex infection strategies, and recent research reveals striking convergences between these viral groups despite their distinct evolutionary origins. Virus factories and phage nuclei separate transcription from translation, mediate spatiotemporal regulation of infection, and involve elaborate interactions with host cytoskeletal systems. Moreover, both viral groups harbor an expanded repertoire of genes acquired from cellular hosts, including transcription and translation-related genes and metabolic enzymes, suggesting convergent strategies to optimize host takeover. Additionally, both lineages are embedded in networks of hyperparasitic interactions, including viral parasites and phage satellites, as well as other selfish genetic elements such as transposons and homing endonucleases, which may, in some cases, facilitate genome innovation and provide fitness benefits. The repeated emergence of genome gigantism across diverse viral clades within both the Nucleocytoviricota and Caudoviricetes suggests that selective pressures favoring gene gain, potentially through a genomic accordion mechanism, are widespread. Yet, genome expansions also harbor many features that are lineage-specific and highly context-dependent. This review explores the mechanistic, functional, and evolutionary parallels that shape the biology of genome gigantism in the virosphere.

DOI: https://doi.org/10.1016/j.mib.2026.102741
Front Cell Infect Microbiol. 2026 ;16 1725666

Effect of periodontal therapy on the oral microbiome and lung function: an intervention study.

Anders Røsland, Hesham Amin, Stein Atle Lie, Andrei Malinovschi, Dagmar F Bunæs, Randi J Bertelsen.

   Introduction: The oral cavity harbors over 700 bacterial species, and disruption of this balance can lead to periodontitis, which has been linked to systemic conditions including respiratory disease.
Methods: In this longitudinal clinical trial, 57 never-smoking adults with stage I-II periodontitis underwent full-mouth periodontal disinfection. Airway resistance and subgingival plaque sampling (analyzed by shotgun metagenomics) was measured at baseline and six weeks after therapy.
Results: Periodontal treatment significantly improved clinical periodontal parameters, and was associated with reductions in airway resistance. Microbiome analysis showed a shift from periodontitis-associated taxa, including Prevotella, Porphyromonas, and Tannerella, toward health-associated species such as Actinomyces oris, and Rothia dentocariosa. Higher airway resistance was associated with a greater relative abundance of periodontitis-associated bacteria.
Discussion: Together, findings suggest that periodontal therapy promotes a healthier oral microbiome and is associated with improved lung function in non-smokers with no prior lung disease.

Keywords:  airway resistance; forced oscillation technique; oral-lung axis; periodontal therapy; periodontitis; plaque subgingival microbiome; shotgun metagenomics

DOI:  https://doi.org/10.3389/fcimb.2026.1725666
J Diabetes Sci Technol. 2026 Apr 03. 19322968261432639

Improving Diabetic Foot Care With Infrared Thermography and Artificial Intelligence: A Review.

Pedro Teixeira, Vítor Filipe, Ana Teixeira.

   BACKGROUND: One of the most common consequences in individuals with diabetes is the diabetic foot, which can cause foot ulcers and even lead to limb amputation. Since an increase of the temperature in the plantar region is directly correlated with an increased risk of ulceration, infrared thermography (IRT) has been used in multiple studies as an automatic tool for detecting problems in diabetic foot. Artificial intelligence-based computer-aided diagnosis systems are being more frequently used to improve decision-making and minimize errors. These technologies are designed to increase examination accuracy, consistency in image interpretation, prognosis evaluation support, and examination accuracy. They also have the ability to offer insightful information and help medical professionals to manage diabetic foot issues successfully.
METHODS: In this work, 37 papers that used thermography and artificial intelligence (AI) to identify diabetic foot complications and/or predict the risk of developing diabetic foot are analyzed.
RESULTS: The results demonstrate the potential of IRT imaging implementation with AI for the identification and prediction of diabetic foot complications.
CONCLUSIONS: The combination of IRT and AI shows significant potential for diabetic foot assessment; however, the great majority of these studies show that the research is confined to classification of foot thermograms using pre-prepared data sets. In particular, there is limited research on segmentation methods and constraints in the use of deep learning due to the lack of large and diverse datasets.

Keywords:  deep learning; diabetic foot; machine learning; neural network; thermography

DOI:  https://doi.org/10.1177/19322968261432639
mSphere. 2026 Apr 02. e0070225

Pseudomonas aeruginosa lasR mutants resist phagocytosis and alter inflammatory cytokine production by cystic fibrosis macrophages.

Daniel S Aridgides, Diane L Mellinger, Lorraine L Gwilt, Anthony R Correia, Carson E Finger, Jay Goddard, Thomas H Hampton, Dallas L Mould, Deborah A Hogan, Alix Ashare.

  Cystic fibrosis (CF) is characterized by chronic muco-obstructive lung disease and infection. People with CF (pwCF) are often colonized with Pseudomonas aeruginosa for years to decades, allowing for evolutionary adaptation. In chronic P. aeruginosa lung isolates from pwCF, the quorum-sensing regulator LasR is frequently nonfunctional; however, the factors enabling lasR loss-of-function (LOF) mutant selection are incompletely understood. We hypothesized that LOF mutations in lasR could allow P. aeruginosa to resist the selective pressure of phagocytosis. We found that in multiple strain backgrounds, LasR LOF decreased phagocytosis by both model THP-1 and primary monocyte-derived macrophages, and lasR complementation increased phagocytosis in mutant strains. While exogenous administration of the quorum-sensing autoinducer 3-oxo-C12-homoserine-lactone, which is made by an enzyme regulated by LasR activity, inhibited phagocytosis and mitochondrial respiration, the phagocytosis resistance seen with lasR mutants appears to be bacterial cell intrinsic rather than due to secreted factors. Finally, we found that lasR LOF mutations altered the inflammatory profile upon infection of CF macrophages, with a shift from IL-1 family cytokine expression toward canonical inflammatory markers, including IL-6 and TNFα. Collectively, these data provide a potential explanation for both the prevalence of lasR mutants in the CF lung as well as their association with worse outcomes.IMPORTANCECystic fibrosis (CF) is a genetically inherited disease that leads to chronic lung infections. Pseudomonas aeruginosa is often implicated in the worsening of lung disease, and it evolves in the lung over time to resist eradication. One of the most commonly disrupted genes in P. aeruginosa isolates from chronically infected CF lungs is lasR, which encodes a transcription factor that regulates multiple virulence factors. What contributes to the apparent fitness of lasR mutants in the CF lung is not well known. Our study shows that lasR loss-of-function mutants resist phagocytosis by macrophages, one of the fundamental mechanisms of clearance by the immune system. We identify mechanisms promoting resistance to phagocytosis and explore the downstream consequences on inflammatory responses. Understanding why lasR mutations arise could inform strategies to eradicate them from the CF lung and improve outcomes.

Keywords:  Pseudomonas aeruginosa; adaptive mutations; host-pathogen interactions; innate immunity; phagocytosis; quorum sensing

DOI:  https://doi.org/10.1128/msphere.00702-25
Int Forum Allergy Rhinol. 2026 Mar 31.

Interspecies Biofilm Dynamics Among Staphylococci: Inflammatory Contributions to Chronic Rhinosinusitis.

Sintayehu Ambachew, Mahnaz Ramezanpour, Clare M Cooksley, Sholeh Feizi, Muhammed Awad, Kevin Aaron Fenix, Peter-John Wormald, Alkis J Psaltis, Sarah Vreugde.

   INTRODUCTION: Staphylococcus species are frequently isolated from the sinonasal niche of chronic rhinosinusitis (CRS) patients. While Staphylococcus aureus is often associated with recalcitrant CRS, Staphylococcus epidermidis and Staphylococcus lugdunensis are largely deemed commensal. The purpose of this study was to investigate interspecies interactions and how those might influence inflammation and susceptibility to antibiotics.
METHODS: Twelve staphylococcal isolates were harvested from six CRS patients, each infected with S. aureus and S. epidermidis, or with S. aureus and S. lugdunensis. Bacteria were cultured to allow biofilm formation in direct and indirect interspecies interactions, followed by measuring their biofilm biomass, antibiotic sensitivity, and toxicity and inflammatory potential when applied to human nasal epithelial cells (HNECs).
RESULTS: S. epidermidis produced up to 7.4-fold higher biomass than S. aureus in monocultures, with a reduction in S. epidermidis biomass under indirect coculture conditions with S. aureus biofilm (p < 0.05). In contrast, the biofilm biomass values of both S. lugdunensis and S. aureus were higher under indirect coculture conditions compared to monocultures for 2/3 paired isolates (p < 0.05). S. epidermidis monocultures and S. aureus/S. epidermidis cocultures were less toxic to HNECs than S. aureus monocultures. S. aureus and S. lugdunensis monocultures and S. aureus/S. lugdunensis cocultures induced interleukin-6 (IL-6) and toxicity to a similar extent versus controls. An increased tolerance to amoxicillin was observed for 2/3 S. epidermidis biofilm and for 3/3 S. lugdunensis biofilm when in indirect contact with S. aureus biofilm (p < 0.05).
CONCLUSION: Overall, staphylococcal interactions were highly strain specific, with S. aureus influencing the biofilm-forming capacity and increasing the tolerance to amoxicillin of both S. epidermidis and S. lugdunensis. S. epidermidis but not S. lugdunensis could mitigate S. aureus induced epithelial cytotoxicity. These findings support the complex nature of interactions among staphylococci with S. aureus and potentially S. lugdunensis having a pathogenic role and S. epidermidis a protective role within polymicrobial biofilms. Our findings have implications for the inflammatory potential and response to therapy of mixed biofilms.

Keywords:  S. aureus; S. epidermidis; S. lugdunensis; biofilm; biomass; chronic rhinosinusitis

DOI:  https://doi.org/10.1002/alr.70148
Microb Drug Resist. 2026 Apr 01. 10766294261430068

Pyelonephritis Caused by Pseudomonas aeruginosa: From Treatable Infection to Therapeutic Dead-End, Rescued by an Investigational Antibiotic.

Bhavik Thacker, Surabhi Madan, Dhara Pethani, Parth Nathwani, Bhavini Shah, Kirtan Shah, Balaji Veeraraghavan.

  Pseudomonas aeruginosa is a major Gram-negative pathogen causing diverse infections, including complicated urinary tract infections (cUTIs). Although such cUTIs are usually treatable with standard antipseudomonal β-lactams, the rise of carbapenem-resistant P. aeruginosa, particularly those producing New Delhi metallo-β-lactamase (NDM), has made therapeutic options extremely limited. We report a 58-year-old man with diabetes, hypertension, and ischemic heart disease who presented with pyelonephritis in the setting of a long-retained ureteric stent. Urine culture grew P. aeruginosa resistant to meropenem, and molecular testing confirmed the presence of NDM. The whole-genome sequencing revealed that the isolate belonged to high-risk sequence type 308 clone carrying NDM-1 and multiple additional resistance determinants. Given the lack of effective alternative antibiotics and the patient's deteriorating clinical course with underlying renal impairment precluding the use of colistin, investigational drug cefepime/zidebactam (WCK 5222) was initiated under compassionate ground. The patient underwent source control with percutaneous nephrostomy and stone clearance. He received 37 days of cefepime/zidebactam, during which he showed rapid clinical improvement, resolution of pyelonephritis, and sterile urine cultures. This case underscores how infections such as cUTI or pyelonephritis, usually considered manageable, can become untreatable in NDM-endemic settings and highlights cefepime/zidebactam as a promising therapeutic option for highly resistant P. aeruginosa.

Keywords:  India; NDM; P. aeruginosa; WCK 5222; cefepime/zidebactam; compassionate-use; pyelonephritis

DOI:  https://doi.org/10.1177/10766294261430068
NPJ Antimicrob Resist. 2026 Apr 02. pii: 21. [Epub ahead of print]4(1):

Selection of porin and LPS mutants during infection by phage T4 facilitates the emergence of β-lactam resistance in Escherichia coli.

Justine Le-Boulch, Erika Charneau, Anne Chevallereau, Arnaud Gutierrez.

Understanding all sources of selective pressure that contribute to the emergence of antibiotic resistance is essential for developing sustainable antimicrobial strategies. Here, we investigated the interaction between phage T4 and Escherichia coli MG1655 to determine whether mutations conferring phage resistance also shape the genetic background for β-lactam resistance. Using experimental evolution, whole-genome sequencing, and targeted genetic reconstructions, we identified mutations in porins and lipopolysaccharide (LPS) biosynthesis as the predominant routes to phage T4 resistance. Precise allelic replacements and isogenic strain comparisons demonstrated that these mutations not only protect against phage predation but also create a genetic context that facilitates the emergence of β-lactam resistance, including resistance to carbapenems. Together, these findings provide compelling evidence that phage-driven selection can establish bacterial genetic backgrounds predisposed to antibiotic resistance. This work highlights the evolutionary risks associated with phage therapy and underscores the need to account for genetic trade-offs when developing alternative antimicrobial strategies.

DOI: https://doi.org/10.1038/s44259-026-00193-9