bims-fagtap 2025-10-05 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–10–05
24 papers selected by
Luca Bolliger, lxBio

A case report of bacteriophage therapy for the treatment of lung infection due to carbapenem-resistant Pseudomonas aeruginosa.
A link to the past: classical phage ISP infects the recently described Staphylococcus borealis species.
Biomaterial-driven innovations in phage therapy: Current strategies and future perspectives.
Phage-Microbiota Interactions in the Gut: Implications for Health and Therapeutic Strategies.
Engineered bacteriophages for therapeutic and diagnostic applications.
Staphylococcus aureus adaptation to vancomycin influences phage susceptibility.
The role of innate immunity, antibiotics, and bacteriophages in the course of bacterial infections and their treatment.
Isolation and characterization of strictly lytic bacteriophages against carbapenem-resistant Enterobacter cloacae complex.
Successful phage therapy in a patient with prosthetic joint infection.
Acinetobacter phages use distinct strategies to breach the capsule barrier.
Metagenome-inspired libraries to engineer phage M13 for targeted killing of Gram-negative bacterial species.
Broad-host-range bacteriophages CBP1 and CBP2 with dual-species activity against Campylobacter jejuni and Campylobacter coli.
Smart Hydrogels in Wearable Electronics for Wound Treatments.
Innovative Approaches to Combat Antimicrobial Resistance: A Review of Emerging Therapies and Technologies.
AI has designed thousands of potential antibiotics. Will any work?
Artificial Intelligence for Postoperative Wound Monitoring: An Integrative Review of Digital Innovation and Clinical Feasibility.
A generative artificial intelligence approach for the discovery of antimicrobial peptides against multidrug-resistant bacteria.
Revolutionizing IBD therapy: Insights into contemporary treatment strategies.
Advancements in research leveraging phage display technology for gastric cancer diagnosis and treatment.
Cell and gene therapy approvals in Asia: regulatory landscape, access and affordability.
Complications in Wound Management.
The Role of Viruses in the Pathogenesis of Periodontitis.
Community-acquired bacterial meningitis in Southern Sweden 2013-2023: a population-based study of incidence, aetiology and diagnostic yield.
Catalyzing Change: Entrepreneurs from the Global South Leading the Fight against Antimicrobial Resistance.

Sci Rep. 2025 Sep 29. 15(1): 33512

A case report of bacteriophage therapy for the treatment of lung infection due to carbapenem-resistant Pseudomonas aeruginosa.

Yongqing Yang, Xin Tan, Min Xiong, Ziqiang Liu, Shitong Lu, Haojie Ge, Ruyue Gao, Jieqiong Zhang, Xiangying Luo, Caiyun Zhou, Shujiang Wei, Xunmei Ding, Yu-E Zhou, Ning Zhou, Jialin Yu, Yingfei Ma, Yongjun Pan.

  In recent years, with the increasing global antimicrobial resistance, bacteriophage therapy has emerged as one of the most promising alternatives to antibiotics. Numerous studies have reported the effectiveness and safety of phage therapy in treating multidrug-resistant bacterial infections. However, there is limited research on the relationship between the emergence of phage-resistant strains and clinical outcomes. In this study, we applied phage nebulization therapy to a patient with carbapenem-resistant Pseudomonas aeruginosa lung infection. After 8 weeks of treatment with P. aeruginosa phages, the patient's sputum bacterial load decreased, overall inflammatory markers decreased, and lung effusion significantly reduced despite isolation of phage-resistant strains. Whole-genome sequencing of resistant isolates, coupled with Galleria mellonella larvae infection modeling, revealed a trade-off effect, demonstrating attenuated virulence associated with phage resistance. This finding underscores the potential for phage therapy to achieve positive clinical outcomes even in the face of resistance development, highlighting the need for a nuanced understanding of phage-bacteria coevolution in clinical settings.

Keywords:   Pseudomonas aeruginosa ; Bacteriophage therapy; Lung infection; Multidrug-resistant bacteria

DOI:  https://doi.org/10.1038/s41598-025-17510-3
Virol J. 2025 Sep 29. 22(1): 308

A link to the past: classical phage ISP infects the recently described Staphylococcus borealis species.

Arthur Kruse Sørensen, Jeroen Wagemans, Md Sabuj Hosen, Hermoine Jean Venter, Jorunn Pauline Cavanagh, Klara Stensvåg, Rob Lavigne, Gabriel Magno de Freitas Almeida.

   BACKGROUND: Staphylococcal infections, caused by a large variety of species within the Staphylococcus genus, are a threat to human health. Although antibiotics are the current choice of treatment for these infections, bacteriophage (phage) therapy has been used with success against Staphylococcus since the dawn of phage therapy. In 2020 a new coagulase-negative species named Staphylococcus borealis was described in Norway. In this study, we focused on understanding phage infections in S. borealis.
METHODS: First, we predict the presence of prophages and phage-defence mechanisms in the genomes of a collection of twelve S. borealis strains by bioinformatics. We also attempted to isolate S. borealis-infecting phages from Norwegian samples and tested the host-range of three known staphylococcal phages against a panel of fifty Norwegian staphylococcal strains.
RESULTS: The presence of prophages and phage defence systems was verified in all tested S. borealis strains. No local Norwegian phages could be obtained in a phage isolation attempt targeted towards S. borealis. The host range analysis shows that phage ISP, originally isolated in the 1920s and still used for phage therapy to date, can infect S. capitis and the S. borealis Hus23 strain. Phage ISP was shown to limit S. borealis Hus23 growth in liquid cultures and lower the formation of biofilm by the bacterium. The efficiency of plating of phage ISP can be improved by repeated passages in the new S. borealis Hus23 host.
CONCLUSIONS: here we expand the known host range of the traditional phage ISP by showing that it also infects S. borealis and can be adapted to the new host by serial passages, showcasing the flexibility of phages as an antimicrobial strategy.

Keywords:   Staphylococci ; Staphylococcus borealis ; Host range; Phage ISP; Phage therapy; Phages

DOI:  https://doi.org/10.1186/s12985-025-02935-z
Microbiol Res. 2025 Sep 24. pii: S0944-5013(25)00310-6. [Epub ahead of print]302 128351

Biomaterial-driven innovations in phage therapy: Current strategies and future perspectives.

Zihe Zhou, Mengzhe Li, Hanyu Fu, Zhongyu Han, Zhenchao Wu, Huahao Fan, Ning Shen, Jiajia Zheng.

  The escalating threat of antimicrobial resistance underscores the urgent need for innovative therapeutic strategies. Phage therapy has experienced a resurgence over the past five years following a prolonged period of neglect during the antibiotic era. Despite its therapeutic promise, critical barriers impede clinical translation, including susceptibility to interference from the host's complex physiological environment, a narrow host range, and the inability to lyse intracellular bacteria. To address these limitations and optimize the efficacy of phage-mediated treatment, recent research has increasingly focused on biomaterial-assisted approaches aimed at enhancing therapeutic efficacy. In this review, we concentrate on recent progress in biomaterial-assisted phage-based treatment strategies, including phage physical encapsulation strategies and phage surface chemical coupling strategies. Physical encapsulation employs liposomes, hydrogels, pH-sensitive polymers and etc. for controlled phage delivery, while surface chemical coupling modifies phage capsids with photosensitizers, nanozymes, or metal nanoparticles to enable multifunctional bactericidal mechanisms. In addition, accessibility for phage therapy of intracellular bacteria is discussed. We also conclude key biomaterial selection criteria-prioritizing biosafety, biodegradability, and microenvironment adaptability, and offer novel perspectives for advancing therapeutic precision as well as multidimensional innovation in combating antimicrobial resistance.

Keywords:  Antimicrobial resistance; Intracellular bacteria; Nanomaterials; Phage therapy; Reactive oxygen species

DOI:  https://doi.org/10.1016/j.micres.2025.128351
Probiotics Antimicrob Proteins. 2025 Oct 01.

Phage-Microbiota Interactions in the Gut: Implications for Health and Therapeutic Strategies.

Ramtin Naderian, Farnaz Alibabaei, Elham Paraandavaji, Parmida Dehghan, Majid Eslami.

  The diversified ecology of microorganisms, including bacteria, archaea, fungi, protozoa, and viruses known collectively as the gut microbiota, which includes bacteriophages, is crucial to human health because it affects functions like immune system regulation, vitamin production, and pathogen protection. Bacteriophages are viruses that infect bacteria and are increasingly recognized as a viable treatment option for antibiotic-resistant strains, owing to their high host specificity, which enables precise targeting of drug-resistant bacteria while sparing commensal microbiota. The complex relationships between bacteriophages and gut microbiota are examined, with emphasis on their roles in maintaining health and contributing to disease. Gut microbiota homeostasis is influenced by a number of factors, including age, nutrition, and drugs. Bacteriophages, via lytic cycles and lysogenic conversion, influence the gut microbiota composition and microbial community structure. Gaining an understanding of these processes is crucial to appreciating their contribution to the stability and variety of microbes. Recent research highlights the gut phageome's potential for therapeutic interventions by demonstrating its substantial influence on immunological responses and metabolic problems. The study of phage-microbiota interactions has been transformed by cutting-edge technologies, including high-throughput sequencing, CRISPR-Cas systems, and viral metagenomics, which allow for thorough research and the creation of new therapeutics. Even though tailored medicine and pathogen management hold great potential, obstacles such as regulatory difficulties and bacterial resistance call for additional investigation. Phage-based therapeutic strategies are rapidly advancing, ranging from genetically engineered phages and phages with modified capsid proteins designed to enhance efficacy to phage cocktails that target multiple bacterial strains.

Keywords:  Bacteriophages; Gut microbiota; Immune modulation; Microbial diversity; Phage therapy

DOI:  https://doi.org/10.1007/s12602-025-10784-z
Dis Model Mech. 2025 Sep 01. pii: dmm052393. [Epub ahead of print]18(9):

Engineered bacteriophages for therapeutic and diagnostic applications.

Kandas Traore, Damien Seyer, Agnes Mihajlovski, Antonia P Sagona.

  Antimicrobial resistance represents one of the most serious threats to both public health and economic sustainability. One of the promising approaches to address this problem is phage therapy - treatment of pathogenic bacterial infections using bacteriophages. Bacteriophages have a narrow host spectrum of activity, minimal side effects and self-replication at the infection site, which positions them as promising candidates to complement or replace conventional antibiotics. Moreover, they can be easily genetically modified to enhance their effectiveness and safety. In this At a Glance article, we highlight the timely relevance of engineered phages as an innovative solution in a rapidly evolving healthcare landscape. First, we introduce bacteriophages' life cycle, ecology and therapeutic history, emphasizing their role in One Health strategies. Then, we describe advanced engineering techniques that can be used to expand bacteriophages' functionalities. Finally, we discuss innovative applications of engineered bacteriophages in biotechnological applications and as a potential countermeasure for antimicrobial resistance, including serving as a shuttle for delivering genes and drugs to the targeted bacterial and eukaryotic cells, targeting intracellular bacteria, contributing to vaccine development, facilitating advancements in tissue engineering and improving bacteriophages' antibacterial properties.

Keywords:  Antibiotic resistance; Bacteriophages; Genomic engineering; Nanomedicine

DOI:  https://doi.org/10.1242/dmm.052393
Res Microbiol. 2025 Sep 26. pii: S0923-2508(25)00076-2. [Epub ahead of print] 104341

Staphylococcus aureus adaptation to vancomycin influences phage susceptibility.

Jack Å H Abrahamsson, Esther Lehmann, Anaëlle Fait, Rob van Dalen, Nina M van Sorge, Hanne Ingmer.

  Phages are bacterial viruses considered as therapeutics for treatment of serious infections with antibiotic-resistant pathogens. In Staphylococcus aureus, resistance to cell wall targeting antibiotics is common in the methicillin resistant (MRSA) or vancomycin-intermediate susceptible (VISA) strains. Furthermore, the cell wall anchors the primary phage receptor, the wall teichoic acid (WTA) glycopolymers. Here we demonstrate that mutations resulting in VISA development affect phage susceptibility of clinically and laboratory evolved strains. For clinical strains we observed both increased and decreased susceptibility compared to the ancestral vancomycin susceptible strains when infected with the therapeutically relevant myoviruses, ΦIPLA-RODI, Stab20, Stab21 and ΦK. For laboratory strains adapted to vancomycin from the MRSA strain, JE2, we observed variable resistance development to the phages ΦIPLA-RODI, Stab21 and ΦK with one strain becoming completely phage resistant. In contrast, half of the VISA strains became susceptible to Stab20 to which JE2 is resistant. These changes in part correlated with altered WTA glycosylation patterns as shown by WTA-specific antibodies and for the resistant strain resulted in compromised phage therapy as shown in a Galleria mellonella infection model. This study highlights the need for understanding antibiotic-driven alterations in bacterial physiology when developing phage-based therapies using combination treatments with antibiotics and phages.

Keywords:  Galleria mellonella; Staphylococcus aureus; VISA; WTA; phage therapy; virulence

DOI:  https://doi.org/10.1016/j.resmic.2025.104341
Proc Natl Acad Sci U S A. 2025 Oct 07. 122(40): e2507914122

The role of innate immunity, antibiotics, and bacteriophages in the course of bacterial infections and their treatment.

Brandon A Berryhill, Teresa Gil-Gil, Christopher Witzany, David A Goldberg, Nic M Vega, Roland R Regoes, Bruce R Levin.

  Critical to our understanding of infections and their treatment is the role the innate immune system plays in controlling bacterial pathogens. Nevertheless, many in vivo systems are made or modified such that they do not have an innate immune response. Use of these systems denies the opportunity to examine the synergy between the immune system and antimicrobial agents. In this study, we demonstrate that the larva of Galleria mellonella is an effective in vivo model for the study of the population and evolutionary biology of bacterial infections and their treatment. To do this, we test three hypotheses concerning the role of the innate immune system during infection. We show that i) sufficiently high densities of bacteria are capable of saturating the innate immune system, ii) bacteriostatic drugs and bacteriophages are as effective as bactericidal antibiotics in preventing mortality and controlling bacterial densities, and iii) minority populations of bacteria resistant to a treating antibiotic will not ascend. Using a highly virulent strain of Staphylococcus aureus and a mathematical computer-simulation model, we further explore how the dynamics of the infection within the short term determine the ultimate infection outcome. We find that immune activation in response to high densities of bacteria leads to a strong but short-lived immune response which ultimately results in a high degree of mortality. Overall, our findings illustrate the utility of the G. mellonella model system in conjunction with established in vivo models in studying infectious disease progression and treatment.

Keywords:  Galleria mellonella; Staphylococcus aureus; infection dynamics; innate immunity; model system

DOI:  https://doi.org/10.1073/pnas.2507914122
Microbiol Spectr. 2025 Oct 01. e0083525

Isolation and characterization of strictly lytic bacteriophages against carbapenem-resistant Enterobacter cloacae complex.

Han-Yueh Kuo, Carl Jay Ballena Bregente, Tran Thi Dieu Thuy, Jazon Harl Hidrosollo, Donna May Dela Cruz-Papa, Tracey Antaeus Gutierrez, Yun-Tsung Huang, Yu-Jui Chuang, Po-Ren Hsueh, Cheng-Yen Kao.

  The global surge of carbapenem-resistant Enterobacter cloacae complex (CR-ECC) poses a significant clinical challenge due to limited treatment options. This study aimed to isolate and characterize lytic bacteriophages (phages) targeting CR-ECC. CR-ECC CYEBC080 was used as the bacterial host for isolating lytic phages, and a comprehensive evaluation was conducted on isolated phages, including phage stability under various pH and temperature conditions, host range analysis, killing curves, and therapeutic efficacy in Galleria mellonella larvae and a murine bacteremia model. Twelve lytic phages with distinct random amplified polymorphic DNA patterns were isolated, and transmission electron microscopy confirmed their classification under the Straboviridae family within the Caudoviricetes class. All phages remained stable across pH 3-11 for up to 90 minutes, with an optimal temperature range of 25°C-37°C. Among them, CYPEBC012 exhibited the broadest host range, lysing 93.75% of 80 CR-ECC isolates, while CYPEBC006 displayed the narrowest, lysing only 65%. Whole-genome sequencing revealed 12 phages with linear double-stranded DNA genomes ranging from 177,624 to 180,648 bp. Phage treatment administered at a multiplicity of infection of 10, 1 hour post-infection, significantly improved larval survival at day 7, reaching ≥80% in most groups, except CYPEBC001 (50%) and CYPEBC004 (60%) treatment groups. In CYEBC080-infected mice, CYPEBC012 treatment resulted in 100% survival by day 3 and 80% survival through day 7. Additionally, phage-treated mice exhibited significantly reduced bacterial loads and high phage titers in blood and liver. This study demonstrates the therapeutic potential of CYPEBC012 as a promising strategy against CR-ECC infections, offering an alternative to conventional antimicrobial treatments.
IMPORTANCE: This study identified and characterized lytic bacteriophages targeting carbapenem-resistant Enterobacter cloacae complex, with CYPEBC012 exhibiting the broadest host range and significantly improving survival in a murine bacteremia model. Its stability and efficacy highlight its potential for clinical application. Our findings demonstrate that phage therapy offers a promising alternative to conventional treatments to combat antibiotic-resistant infections.

Keywords:  Enterobacter cloacae complex; bacteriophage; carbapenem resistance; multidrug resistance; whole-genome sequencing

DOI:  https://doi.org/10.1128/spectrum.00835-25
Enferm Infecc Microbiol Clin (Engl Ed). 2025 Oct;pii: S2529-993X(25)00171-6. [Epub ahead of print]43(8): 535-536

Successful phage therapy in a patient with prosthetic joint infection.

Sofía De la Villa, Miguel Cuervo, Pilar Domingo-Calap, Patricia Muñoz.

DOI: https://doi.org/10.1016/j.eimce.2025.05.011
PLoS Pathog. 2025 Sep 29. 21(9): e1013536

Acinetobacter phages use distinct strategies to breach the capsule barrier.

Alexis J McCalla, Forrest C Walker, Fabiana Bisaro, Miguel Rodriguez-Anavitate, Anna Johannesman, Gisela Di Venanzio, Mario F Feldman, Michele LeRoux.

Acinetobacter baumannii is an opportunistic pathogen that is a growing threat in hospital settings due to its alarmingly high rates of antibiotic resistance. Alternative therapies are urgently needed to manage the growing burden of untreatable A. baumannii infections. Phage therapy is a promising avenue that has already seen some success in isolated compassionate-use cases, including the famous "Patterson case". Bacterial surface structures are the first determinants of susceptibility to phage infection and play a major role in phage host range. Most A. baumannii strains produce a protective capsule that is highly diverse both in structure and composition, and provides the first immunity barrier against phages. Here, we perform a detailed molecular characterization of three recently isolated, distinct A. baumannii phages, StAb1, StAb2, and StAb3, that breach the capsule via different mechanisms. Like many previously described A. baumannii phages, a specific capsule type is necessary for StAb1 infection. We found that StAb2 and its relatives adsorb to either a specific capsule type or the conserved outer membrane protein CarO, a porin normally occluded by the capsule. Thus, this phage has a narrow host range amongst capsulated strains, but can broadly infect A. baumannii strains lacking capsule. We also show that StAb3 requires a conserved and uncharacterized glycan that we have termed phage glycan receptor (PGR) that enables StAb3 to infect a broad range of A. baumannii strains irrespective of whether capsule is present. We demonstrate how rationally combining phages with distinct capsule interactions reduces the rapid emergence of phage escape mutants, with potential applications for more effective phage therapy.

DOI: https://doi.org/10.1371/journal.ppat.1013536
Nucleic Acids Res. 2025 Sep 23. pii: gkaf984. [Epub ahead of print]53(18):

Metagenome-inspired libraries to engineer phage M13 for targeted killing of Gram-negative bacterial species.

Yanxi Yang, Dayeon Kang, Beatrice Mihalache, Shelby Vexler, Saumya Jain, Huan Peng, Nasim Annabi, Shangxin Yang, Irene A Chen.

Given concerning trends in antibiotic resistance, phages have been increasingly explored as promising antimicrobial agents. However, a major problem with phage therapy is the overly high specificity of phages for their hosts, which is currently addressed by a personalized approach involving screening a bank of wild-type phages against each clinical isolate. To shorten this process, we propose that a focused library of synthetic phages could be rapidly selected for a member binding to a given clinical isolate. We created libraries of recombinant M13 phages expressing receptor-binding proteins based on the collective metagenome of inovirus phages, a diverse group whose members appear to infect nearly all bacterial phyla. Using two rounds of a pull-down selection, phage variants were identified against several Gram-negative pathogens, including a variant (M13PAB) that bound to several Pseudomonas aeruginosa strains, including clinical isolates. To confer bactericidal activity to the nonlytic phage, a last-line but nephrotoxic lipopeptide, colistin, was cross-linked to the M13PAB virions. The colistin-M13PAB phage conjugate lowered the minimal inhibitory concentration of colistin by 1-2 orders of magnitude for multiple strains of P. aeruginosa and showed a lack of hemolytic or cytotoxic activity in vitro, suggesting high potency combined with low toxicity. Thus, a metagenome-inspired library displayed on the M13 phage scaffold, when subjected to a short selection for binding to a bacterial clinical isolate, could yield a phage variant that targets the specified strain. This approach may improve the speed, consistency, and cost-effectiveness of personalized phage therapy.

DOI: https://doi.org/10.1093/nar/gkaf984
Int J Food Microbiol. 2025 Sep 27. pii: S0168-1605(25)00414-3. [Epub ahead of print]444 111469

Broad-host-range bacteriophages CBP1 and CBP2 with dual-species activity against Campylobacter jejuni and Campylobacter coli.

Eunbyeol Ahn, Jinshil Kim, Joonbeom Kim, Jeong In Hur, Sangryeol Ryu, Byeonghwa Jeon.

  Campylobacter spp., particularly Campylobacter jejuni and Campylobacter coli, are leading causes of foodborne illness worldwide, posing a significant public health challenge. Since the majority of Campylobacter infections are linked to contaminated poultry meat, the development of effective control strategies remains critical for food safety. Bacteriophage (phage) therapy has emerged as a promising biocontrol approach for enhancing food safety, yet its practical application has been limited by the narrow host specificity of most Campylobacter phages, which typically infect only specific strains or a single species. Here, we describe the isolation and characterization of two broad-host-range phages, CBP1 and CBP2, demonstrating remarkable dual-species infectivity against both C. jejuni and C. coli. These phages exhibited high infectivity across a phylogenetically diverse panel of C. jejuni and C. coli isolates from retail raw chicken, encompassing multiple clonal complexes. Notably, CBP1 and CBP2 effectively suppressed the growth of the predominant poultry-associated lineages, including CC-21 in C. jejuni and CC-828 in C. coli. Furthermore, the phages significantly reduced Campylobacter loads on artificially contaminated chicken meat, highlighting their practical potential as biocontrol agents in poultry production. Collectively, these findings demonstrate that CBP1 and CBP2 represent rare broad-host-range phages with dual-species activity, providing a versatile and effective intervention strategy for reducing Campylobacter contamination in poultry production systems.

Keywords:  Broad-host-range phage; Campylobacter; Dual-species antimicrobial; Phage biocontrol; Poultry meat safety

DOI:  https://doi.org/10.1016/j.ijfoodmicro.2025.111469
Small. 2025 Sep 29. e07368

Smart Hydrogels in Wearable Electronics for Wound Treatments.

Boyuan Li, Min Li, Yi Wang.

  The complexity of wound care is a significant clinical challenge today. To address this issue, researchers extensively study hydrogels as a next-generation solution. Hydrogel is a moisture-retaining and biocompatible material that promotes cell regeneration and accelerates wound healing. However, traditional hydrogel dressings focus on passive protection for wounds, lacking dynamic responsiveness, and controllable adjustment capability based on changes in wound condition. Smart hydrogels, especially when integrated with wearable electronics, have emerged as a revolutionary advancement in wound treatment. By incorporating sensing, responsive controlled release, and dynamic interactive design, smart hydrogels enable dynamic wound treatment, demonstrating notable advantages. The advancements of smart hydrogels within the field of wearable electronics are summarized, elucidating their innovative fabrication techniques, critical functional properties, and integration into intelligent wound care systems through wearable technologies. The recent progress of smart hydrogels for wound healing acceleration is emphasized, including the ability to dynamically adapt to the complex wound microenvironment and the role of real-time monitoring of wound biomarkers.

Keywords:  biomaterials; smart hydrogels; wearable electronics; wound healing

DOI:  https://doi.org/10.1002/smll.202507368
Probiotics Antimicrob Proteins. 2025 Sep 30.

Innovative Approaches to Combat Antimicrobial Resistance: A Review of Emerging Therapies and Technologies.

Mujeeb Ur Rahman, Junaid Ali Shah, Muhammad Nadeem Khan, Hazrat Bilal, Daochen Zhu, Zongjun Du, Da-Shuai Mu.

  The threat of antimicrobial resistance (AMR) presents a challenge in infectious diseases, leading to higher illness and deaths worldwide. No new antibiotic has been introduced, leaving healthcare systems vulnerable to resistant pathogens. Researchers are exploring innovative approaches to overcome this growing resistance crisis. One promising strategy is synergistic therapy using combined drugs to enhance efficacy and reduce resistance. Other approaches focus on targeting the specific enzymes or proteins responsible for resistance mechanisms, thereby neutralizing the defense strategies of microorganisms. Advances in drug delivery systems have also shown promise in improving the effectiveness of existing antimicrobial agents. Biotechnological breakthroughs, such as bacteriophages and antibodies, have seen partial clinical implementation, while newer approaches like antimicrobial peptides (AMPs), lysins, and probiotics are still under development. Emerging technologies such as CRISPR-Cas and engineered phages demonstrate significant potential in preclinical studies, offering precision targeting of resistance genes and pathogen-specific lysis, respectively. However, their translational success hinges on overcoming delivery challenges, scalability, and regulatory hurdles. Additionally, physicochemical methods that disrupt microbial activity are being explored as alternative treatments. While innovative therapies like phage-derived lysins and CRISPR-Cas systems show promise in preclinical models, their clinical impact remains to be validated through large-scale trials. Their integration into mainstream medicine will depend on addressing practical challenges such as manufacturing consistency, cost considerations, and real-world efficacy assessments. These efforts are crucial for addressing the growing threat of AMR and advancing more effective, sustainable infection control strategies in clinical settings.

Keywords:  Antimicrobial peptides; Antimicrobial resistance; CRISPR-Cas technology; Combination therapy; Genetically modified phages

DOI:  https://doi.org/10.1007/s12602-025-10676-2
Nature. 2025 Oct 03.

AI has designed thousands of potential antibiotics. Will any work?

Rachel Fieldhouse.



Keywords:  Antibiotics; Infection; Machine learning

DOI:  https://doi.org/10.1038/d41586-025-03201-6
Am Surg. 2025 Sep 30. 31348251385104

Artificial Intelligence for Postoperative Wound Monitoring: An Integrative Review of Digital Innovation and Clinical Feasibility.

Joel Grunhut, Khanjan Nagarsheth.

  Artificial intelligence (AI) has transformative potential in postoperative wound care through precise, automated, and timely wound assessment, yet specific applications to surgical wounds remain relatively unexplored compared to chronic wound care. This integrative review critically assesses the state-of-the-art in AI-driven postoperative wound monitoring, highlighting significant advancements, existing limitations, and opportunities for future development. Following an extensive literature search of PubMed, Google Scholar, and Medline, we identified 118 relevant articles meeting stringent inclusion criteria. Our analysis underscores the critical need for large-scale, standardized datasets, explainable AI frameworks, and robust clinical validation studies. By evaluating AI technologies-such as deep learning, wearable biosensors, mobile applications, and natural language processing-we propose a roadmap for integrating advanced AI methods into surgical practice, aiming ultimately to enhance clinical outcomes and patient care.

Keywords:  artificial intelligence; colorectal; surgical infection; vascular surgery; wound healing

DOI:  https://doi.org/10.1177/00031348251385104
Nat Microbiol. 2025 Oct 03.

A generative artificial intelligence approach for the discovery of antimicrobial peptides against multidrug-resistant bacteria.

Yihui Wang, Lanlan Zhao, Ziyun Li, Yaxuan Xi, Yingmiao Pan, Guoping Zhao, Lei Zhang.

The discovery of novel antimicrobial peptides (AMPs) against clinical superbugs is urgently needed to address the ongoing antibiotic resistance crisis. AMPs are promising candidates due to their broad-spectrum activity, rapid bactericidal mechanisms and reduced likelihood of inducing resistance compared with conventional antibiotics. Here, a pre-trained protein large language model (LLM), ProteoGPT, was established and further developed into multiple specialized subLLMs to assemble a sequential pipeline. This pipeline enables rapid screening across hundreds of millions of peptide sequences, ensuring potent antimicrobial activity and minimizing cytotoxic risks. Through transfer learning, we endowed the LLMs with different domain-specific knowledge to achieve high-throughput mining and generation of AMPs within a unified methodological framework. Notably, both mined and generated AMPs exhibited reduced susceptibility to resistance development in ICU-derived carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA) in vitro. The AMPs also showed comparable or superior therapeutic efficacy in in vivo thigh infection mouse models compared with clinical antibiotics, without causing organ damage and disrupting gut microbiota. The mechanisms of action of these AMPs involve disruption of the cytoplasmic membrane and membrane depolarization. Overall, this study presents a generative artificial intelligence approach for the discovery of novel antimicrobials against multidrug-resistant bacteria, enabling efficient and extensive exploration of AMP space.

DOI: https://doi.org/10.1038/s41564-025-02114-4
Int Rev Immunol. 2025 Sep 30. 1-25

Revolutionizing IBD therapy: Insights into contemporary treatment strategies.

Pooja Kushwaha, Rahila Qureshi, Nooruddin Khan, Sangita Mukhopadhyay.

  Inflammatory bowel disease (IBD) varies in prevalence globally. Recent rise in IBD cases mirrors evolving health landscape due to urbanization and lifestyle changes worldwide. Existing drugs for IBD include aminosalicylates, corticosteroids, Immunomodulators, biologics, JAK inhibitors, and antibiotics. Although these medications are effective in managing symptoms and remission, these present several with limitations. Side effects such as nausea, infections, and liver toxicity are common, and some patients may develop resistance or lose response over time. Additionally, biologics can be costly, and immunosuppressive drugs raise concerns about long-term safety along increased risk of infection. Importantly, approximately 10% to 30% of the IBD patients do not respond to conventional treatments such as corticosteroids, immunosuppressants, or biologic therapies. Research continues to explore new treatments to address these limitations and improve outcomes for individuals with IBD. This review is an attempt to critically evaluate the currently available treatments for IBD underlining their limitations, and the pressing demand for innovative strategies. Further, we delve into the rationale behind peptide-based therapies, emphasizing their potential to modulate inflammation and promote mucosal healing. The work also highlights promising outcomes from recent preclinical and clinical studies underscoring the pivotal role of peptides in IBD management.

Keywords:  Clinical trials; drugs/therapeutics; inflammatory bowel disease; synthetic peptides; treatment strategies

DOI:  https://doi.org/10.1080/08830185.2025.2563522
Front Microbiol. 2025 ;16 1632560

Advancements in research leveraging phage display technology for gastric cancer diagnosis and treatment.

Zhenyu Wang, Yuping Li, Jun Lin, Fuyu Deng, Yao Liu, Yuan Ji.

  Gastric cancer persists as a major global health challenge, ranking among the leading causes of cancer-related deaths worldwide. The high mortality rate primarily stems from difficulties in early detection, often resulting in late-stage diagnosis when treatment options are limited. Phage display technology, developed in 1985, has emerged as a powerful tool in gastric cancer research, facilitating significant advances in three key areas: (1) identification of novel biomarkers for early detection, (2) screening of targeted therapeutic molecules, and (3) development of diagnostic reagents. This comprehensive review examines current applications of phage display in both diagnostic and therapeutic approaches for gastric cancer, while critically analyzing existing limitations in sensitivity, specificity, library diversity, and screening efficiency. Furthermore, we discuss the promising potential of integrating phage display with other cutting-edge technologies, proposing future research directions that could enhance its clinical utility and ultimately improve patient outcomes in gastric cancer management.

Keywords:  Treatment; biomarker; diagnosis; gastric cancer; phage display; targeting

DOI:  https://doi.org/10.3389/fmicb.2025.1632560
Cytotherapy. 2025 Aug 22. pii: S1465-3249(25)00810-2. [Epub ahead of print]

Cell and gene therapy approvals in Asia: regulatory landscape, access and affordability.

William Ying Khee Hwang, Sudipto Bari, Shin Kawamata, Bryan Choi, Chaiyong Koaykul, He Huang, Pawan Gupta.

  Cell and gene therapies (CGTs) are revolutionizing the treatment paradigm for a range of life-threatening and rare conditions, offering curative potential where conventional therapies have fallen short. In Asia, the CGT landscape has matured significantly in recent years, driven by regulatory reforms, increased local development and a growing number of product approvals. This updated review presents a comprehensive analysis of CGT regulatory frameworks, product approvals, pricing trends and reimbursement policies across six key Asian markets: Singapore, Japan, South Korea, China, India and Thailand. Drawing upon updated data from 2023 to 2025, we examine differences in regulatory maturity, access pathways, affordability and local manufacturing capabilities. The review highlights how certain countries, such as Japan and South Korea, have successfully implemented fast-track regulatory pathways, while others, like India and China, have emphasized domestic innovation to drive down costs. Despite progress, affordability, scalability and sustainable reimbursement remain persistent challenges. By presenting an up-to-date comparative analysis and synthesizing emerging policy innovations, this article offers insights into opportunities for harmonization, equitable access and future policy planning in Asia's rapidly evolving CGT sector.

Keywords:  Asia; CTGTP; approvals; funding; regulatory

DOI:  https://doi.org/10.1016/j.jcyt.2025.08.005
Vet Clin North Am Equine Pract. 2025 Sep 30. pii: S0749-0739(25)00049-5. [Epub ahead of print]

Complications in Wound Management.

Francisco J Morales Yñiguez, Britta S Leise.

  Over 25% of all emergencies are classified as wounds, making them the most common health conditions treated by veterinarians. While equine wounds may heal with minimal intervention, many complications associated with wound management can occur, thereby delaying wound healing and leading to chronic non-healing wounds. Wounds should be closed primarily when possible; however, numerous factors influence the risk of complications. Infection and biofilm production are common causes of delayed wound healing. Other causes of non-healing wounds include the presence of foreign material, sequestrum formation, the development of exuberant granulation tissue, neoplastic transition, and habronemiasis.

Keywords:  Biofilm; Dehiscence; Exuberant granulation tissue; Infection; Neoplastic transformation; Nonhealing chronic wounds; Sequestrum

DOI:  https://doi.org/10.1016/j.cveq.2025.08.006
J Periodontal Res. 2025 Sep 29.

The Role of Viruses in the Pathogenesis of Periodontitis.

K N Stolte, J Slots, H Dommisch.

  Periodontitis is a multifactorial inflammatory disease, traditionally attributed to a bacterial biofilm. Increasing evidence indicates that viruses, especially members of the Herpesviridae family, are frequently detected in periodontal lesions and may influence disease onset and progression. This review provides an overview of viruses present in the oral cavity, including Herpesviridae, Papillomaviridae, Retroviridae, SARS-CoV-2, and emerging viral taxa such as Redondoviridae and bacteriophages, and summarizes their reported associations with periodontitis. Proposed mechanisms of viral contribution include modulation of local immune responses, facilitation of bacterial overgrowth, direct cytopathic effects on periodontal tissues, and synergistic interactions with classical periodontal pathobionts. Clinical correlations link viral load and co-infections with increased disease severity. Identification of direct causal relationships and therapeutic aspects, such as antiviral and combined antimicrobial approaches, is the subject of current research; however, clinical evidence remains limited. Overall, specific viruses show direct influence on periodontal bacterial pathogens and affect the host immune response, warranting further longitudinal and functional studies to clarify their exact role in periodontitis onset, progression, and treatment.

Keywords:  herpesvirus; infection; inflammation; pathogenesis; periodontitis; virus

DOI:  https://doi.org/10.1111/jre.70039
Eur J Clin Microbiol Infect Dis. 2025 Oct 01.

Community-acquired bacterial meningitis in Southern Sweden 2013-2023: a population-based study of incidence, aetiology and diagnostic yield.

Tobias West, Robin Carlander, Torgny Sunnerhagen, Gustav Torisson, Oskar Ljungquist.

   PURPOSE: Despite advances in medical care, bacterial meningitis still poses a considerable health issue from a global perspective. An ageing population and increasing development and use of vaccines are likely to affect the incidence and aetiology. The aim of this study was to describe the incidence and aetiology of community-acquired bacterial meningitis (CABM) in our setting, as well as the serotypes of Streptococcus pneumoniae and Neisseria meningitidis causing CABM, in relation to available vaccines.
METHOD: Patients of all ages with CABM in southern Sweden 2013-2023 were included. Patients were identified through records of cerebrospinal fluid tests from the Department of Clinical Microbiology, and through International Classification of Diseases 10 codes for bacterial meningitis. Age-standardised incidence rates were calculated based on the European Standard Population 2013.
RESULTS: During the study period, 244 episodes of CABM in 238 individuals were identified. Definitive aetiology could be established in 93% of episodes. Mean incidence rate was 1.63 per 100,000 person-years, with a trend of declining incidence during the study period. Streptococcus pneumoniae was the most common pathogen, accounting for 46.7% of episodes. 63.6% of the episodes of pneumococcal meningitis were caused by serotypes included in current vaccines.
CONCLUSION: Pneumococcal meningitis is the primary driver of incidence and trends of all-cause community-acquired bacterial meningitis in southern Sweden. Further studies are warranted to investigate how vaccination could influence both disease incidence and shifts in serotype distribution, while also identifying optimal patient populations for targeted interventions.

Keywords:  Aetiology; Bacterial meningitis; Incidence; Serotypes; Temporal trend; Vaccine-preventable

DOI:  https://doi.org/10.1007/s10096-025-05247-w
ACS Infect Dis. 2025 Sep 29.

Catalyzing Change: Entrepreneurs from the Global South Leading the Fight against Antimicrobial Resistance.

Leela Maitreyi, Vasan K Sambandamurthy.

  Antimicrobial resistance (AMR) is rapidly emerging as one of the greatest threats to global health, with projections estimating 10 million deaths annually by 2050. The departure of major pharmaceutical companies from antibiotic research─driven by a combination of scientific complexity, low profitability, and complex regulatory hurdles─has left a serious innovation gap in the development of new antibiotics. This gap is being filled by entrepreneurial ventures in the Global South, particularly in India, South Africa, Brazil, and China, where small and medium enterprises (SMEs) now drive 80% of late-stage antibiotic development. The convergence of abundant scientific talent, cost-effective research capabilities, access to seed funding, and real-world experience with high-burden pathogens is fueling the discovery of innovative solutions to address multidrug-resistant infections. This perspective examines how these vibrant ecosystems are overcoming traditional barriers to innovation by leveraging scientific advancements, tapping into local talent, forming strategic partnerships, and developing novel business models to enable equitable access, thereby realigning public health obligations with commercial viability. This entrepreneurial endeavor in the Global South not only provides sustainable solutions to local health challenges but also contributes to the creation of a resilient global antibiotic ecosystem.

Keywords:  Global South; antimicrobial resistance; entrepreneurship; equitable access; funding; low-and-middle-income countries (LMICs)

DOI:  https://doi.org/10.1021/acsinfecdis.5c00565