bims-fagtap 2025-06-08 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–06–08
twenty-one papers selected by
Luca Bolliger, lxBio

Fast phages outcompete by depleting host resources.
Large-Scale Genomic Analysis of CpG-Mediated Immunogenicity in Bacteriophages and a Novel Predictive Risk Index.
A solution to the postantibiotic era: phages as precision medicine.
Present and future of microbiome-targeting therapeutics.
Implementation challenges of personalised phage therapy.
Multifunctional Nanocarriers in Bacteriophage Delivery: A Paradigm Shift in Treating Multidrug-Resistant Infections.
Intra-individual diversity of bacteriophage susceptibility in Burkholderia cultured from cystic fibrosis sputum.
Effects of sequential administration of phage cocktail, ciprofloxacin, and caspofungin on Staphylococcus aureus and Candida albicans dual-species biofilms.
Simple, rapid, and efficient purification of M13 phages: The Faj-elek method.
Environmental Phages: Ecosystem Dynamics, Biotechnological Applications and their limits, and Future Directions.
Reversal of phenotypic resistance in multi-drug resistant carbapenemase-producing K. pneumoniae clinical isolates due to in vitro synergistic interactions between bacteriophages and antibiotics at clinically achievable concentrations.
Resistance trend in bacteria isolated from corneal ulcers: A retrospective analysis from Pakistan.
Bacteriophage cocktail LEC2-LEC10 for broad-spectrum control of pathogenic and uncharacterized Escherichia coli in fresh produce.
Alterations of the Enteric Virome in Vogt-Koyanagi-Harada Disease.
An Overview of Novel Formulations For Ocular Viral Infections: Focused On Nanomedicines.
Deep learning-guided structural analysis of a novel bacteriophage KPP105 against multidrug-resistant Klebsiella pneumoniae.
Multiobjective learning and design of bacteriophage specificity.
Phage Display-Selected Peptides: Research and Clinical Applications in Cancer Imaging.
Peptide vaccines: an innovative therapeutic approach against antibiotic-resistant bacterial infections.
Implications of gut microbiota-mediated epigenetic modifications in intestinal diseases.
Understanding Diabetic Wounds: A Review of Mechanisms, Pathophysiology, and Multimodal Management Strategies.

Trends Microbiol. 2025 Jun 03. pii: S0966-842X(25)00158-1. [Epub ahead of print]

Fast phages outcompete by depleting host resources.

Josie Elliott, Anne Chevallereau.

  In nature, phages frequently coinfect bacteria, leading to inter-species competition. Furthermore, phage therapy often involves using a cocktail of different species to circumvent bacterial resistance. Bürkle et al. investigated the competition dynamics between two virulent phages, demonstrating that faster assembly can allow a phage to dominate over its competitor.

Keywords:  phage therapy; phage–bacteria interactions; phage–phage competition

DOI:  https://doi.org/10.1016/j.tim.2025.05.011
bioRxiv. 2025 May 16. pii: 2025.05.15.652987. [Epub ahead of print]

Large-Scale Genomic Analysis of CpG-Mediated Immunogenicity in Bacteriophages and a Novel Predictive Risk Index.

Lukeman Kharrat, Camilo A Garcia-Botero, Wade Ingersoll, Tiffany Luong, Alejandro Reyes, Dwayne R Roach.

  Bacteriophage (phage) therapy is a promising alternative to antibiotics, yet phage-induced immune responses can affect treatment efficacy. However, current methods for assessing phage immunogenicity are limited, hindering the development of safer, more effective therapies. Here, we introduce the Bacteriophage Risk Index (BRI), a novel metric that quantifies phage immunogenic potential based on CpG dinucleotide frequency, motif spacing, and sequence context, key factors influencing Toll-like receptor 9 (TLR9) activation. Applying the BRI to 7,011 phage genomes, we classified them into five risk tiers, revealing substantial immunogenic variability, even among phages targeting the same bacterial host. BRI scores correlated with immune responses in human lung epithelial cells, validating its predictive power. Experimental testing further confirmed this, as exposure of lung epithelial cells to two phages from distinct risk tiers showed that the high-risk phage (Category 4) induced a strong pro-inflammatory response, upregulating CXCL1, CXCL8, IRF7, and TNFAIP3, while the low-risk phage (Category 2) triggered minimal immune activation with limited cytokine expression. These findings confirm that higher BRI scores predict stronger immune responses, providing a robust tool for evaluating phage immunogenicity. By enabling the selection of phages with lower immunogenic potential, the BRI enhances the safety and efficacy of phage therapy while offering a framework for regulatory agencies, clinical researchers, and biologic drug development, with applications extending beyond phage therapy to other immunogenic biologics.

Keywords:  CpG motifs; host-phage interaction; immune response; pattern recognition; phage therapy; safety

DOI:  https://doi.org/10.1101/2025.05.15.652987
Curr Opin Microbiol. 2025 May 30. pii: S1369-5274(25)00035-9. [Epub ahead of print]86 102613

A solution to the postantibiotic era: phages as precision medicine.

Landon J Getz, Pramalkumar H Patel, Karen L Maxwell.

Antibiotic-resistant bacterial infections pose a significant global health challenge. Phage therapy provides a promising alternative to antibiotics that enables the specific targeting of pathogenic bacteria while preserving the healthy microbiome. Recent advances in genetic engineering, synthetic biology, and artificial intelligence have rekindled interest in phage therapy, as they move phages into the realm of precision medicine. Engineered phages can be customized to have a broader host range, encode counter-defenses that overcome bacterial immune systems, or express other proteins that modulate the bacterial host to their advantage. Innovations in artificial intelligence and machine learning promise to speed up the identification of optimal phage candidates and create tailored cocktails for individualized therapies - advances that will transform phage therapy and provide a solution to the antibiotic resistance crisis.

DOI: https://doi.org/10.1016/j.mib.2025.102613
J Clin Invest. 2025 Jun 02. pii: e184323. [Epub ahead of print]135(11):

Present and future of microbiome-targeting therapeutics.

Lauren E Lynch, Rachel Lahowetz, Christian Maresso, Austen Terwilliger, Jason Pizzini, Valeria Melendez Hebib, Robert A Britton, Anthony W Maresso, Geoffrey A Preidis.

A large body of evidence suggests that single- and multiple-strain probiotics and synbiotics could have roles in the management of specific gastrointestinal disorders. However, ongoing concerns regarding the quality and heterogeneity of the clinical data, safety in vulnerable populations, and the lack of regulation of products containing live microbes are barriers to widespread clinical use. Safety and regulatory issues must be addressed and new technologies considered. One alternative future strategy is the use of synthetic bacterial communities, defined as manually assembled consortia of two or more bacteria originally derived from the human gastrointestinal tract. Synthetic bacterial communities can model functional, ecological, and structural aspects of native communities within the gastrointestinal tract, occupying varying nutritional niches and providing the host with a stable, robust, and diverse gut microbiota that can prevent pathobiont colonization by way of colonization resistance. Alternatively, phage therapy is the use of lytic phage to treat bacterial infections. The rise of antimicrobial resistance has led to renewed interest in phage therapy, and the high specificity of phages for their hosts has spurred interest in using phage-based approaches to precisely modulate the microbiome. In this Review, we consider the present and future of microbiome-targeting therapies, with a special focus on early-life applications, such as prevention of necrotizing enterocolitis.

DOI: https://doi.org/10.1172/JCI184323
Lancet. 2025 May 31. pii: S0140-6736(25)00737-8. [Epub ahead of print]405(10493): 1901-1903

Implementation challenges of personalised phage therapy.

Sarah Djebara, Rob Lavigne, Jean-Paul Pirnay.

DOI: https://doi.org/10.1016/S0140-6736(25)00737-8
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2025 May-Jun;17(3):17(3): e70021

Multifunctional Nanocarriers in Bacteriophage Delivery: A Paradigm Shift in Treating Multidrug-Resistant Infections.

Rohit Patil, Sanchit Arora, Dinesh Kumar, Ashish Kumar Agrawal.

  The rising challenge of antibiotic-resistant bacterial infections poses a severe threat to global health, highlighting the urgent need for innovative treatment strategies. Bacteriophages, viruses specifically targeting and destroying bacteria, have emerged as a promising solution. However, their therapeutic application faces significant hurdles, including sensitivity to the immune system, limited stability, and challenges in effectively reaching infection sites. Multifunctional nanocarriers offer a cutting-edge approach to address these limitations. These nanoscale delivery systems protect bacteriophages from degradation, enhance their stability, and enable precise release at the infection site. Certain nanocarriers are engineered to respond to specific physiological conditions, such as pH or temperature, and can be combined with additional therapies, like antibiotics, for synergistic effects. Moreover, they hold the potential for real-time infection tracking and treatment monitoring, aligning with the goals of personalized medicine. This review highlights the synergistic potential of nanotechnology and bacteriophage therapy in combating antibiotic-resistant bacteria. By overcoming critical barriers to bacteriophage application, multifunctional nanocarriers represent a transformative advancement in the fight against drug-resistant infections. Furthermore, their ability to enhance treatment efficacy and outcomes establishes them as an essential innovation in advancing global health solutions.

Keywords:  antibiotic resistance; bacteriophage therapy; multidrug‐resistant infections; multifunctional nanocarriers; targeted drug delivery

DOI:  https://doi.org/10.1002/wnan.70021
J Cyst Fibros. 2025 May 31. pii: S1569-1993(25)01497-3. [Epub ahead of print]

Intra-individual diversity of bacteriophage susceptibility in Burkholderia cultured from cystic fibrosis sputum.

Ortal Yerushalmy, Abby M Korn, Guichun Yao, Ronen Hazan, Carlos F Gonzalez, Jason J Gill, Linda M Kalikin, Theodore Spilker, Lindsay J Caverly, Amy A Bumford, Nathan R Wallace, Saima Aslam, Ran Nir-Paz, Daria Van Tyne, John J LiPuma.

  The use of bacteriophage (phage) to treat bacterial infection of airways in persons with cystic fibrosis (CF) is gaining interest. However, phenotypic diversification of bacteria during chronic airway infection presents a potential challenge to this therapy. We recovered and subcultured two or three Burkholderia colonies from each of 12 CF sputum samples. All isolates were tested for their susceptibility to a panel of 65 Burkholderia-targeting phages. We observed that 9 (75%) of the 12 colony sets comprised mixtures of isolates that were sensitive or resistant to one or more of the phages tested. The occurrence of mixed populations of phage-sensitive and phage-resistant Burkholderia in individuals with CF needs to be considered in the development of phage therapy for this patient population.

Keywords:  Bacteriophage therapy; Burkholderia airway infection; Cystic fibrosis

DOI:  https://doi.org/10.1016/j.jcf.2025.05.008
Microbes Infect. 2025 May 30. pii: S1286-4579(25)00063-2. [Epub ahead of print] 105531

Effects of sequential administration of phage cocktail, ciprofloxacin, and caspofungin on Staphylococcus aureus and Candida albicans dual-species biofilms.

Marta Gliźniewicz, Barbara Dołęgowska, Adrian Augustyniak, Rafał Rakoczy, Tomasz Kędzierski, Ewa Mijowska, Bartłomiej Grygorcewicz.

  Polymicrobial biofilms, including inter-kingdom ones, represent another threat in the post-antibiotic era. Therefore, many alternative solutions are being investigated, including phage-antibiotic synergy (PAS), which may be more effective due to the differing mechanisms of action of drugs and phages. In this study, we evaluated how different sequences of administering a bacteriophage cocktail, ciprofloxacin, and caspofungin affect the eradication of S. aureus and C. albicans in vitro (planktonic culture and in biofilms). In liquid culture, the phage → caspofungin → ciprofloxacin treatment completely eradicated both organisms. In biofilms, the most effective regimens were either the simultaneous application of all three agents or phages + ciprofloxacin followed by caspofungin. Therefore, the sequence of administration of drugs and phages is a key factor in achieving effective therapy and revealing the most synergistic combinations.

Keywords:  Drug resistance; Mixed-species biofilm; Phage therapy; Phage-antibiotic synergy (PAS); Polymicrobial biofilm

DOI:  https://doi.org/10.1016/j.micinf.2025.105531
PLoS One. 2025 ;20(6): e0325621

Simple, rapid, and efficient purification of M13 phages: The Faj-elek method.

Gizem Kılıç, Esma Aybakan, Neda Tatlıoğlu, Gökçen Özgün, Tanıl Kocagöz, Erkan Mozioğlu.

M13 bacteriophages (phages) are used as very important tools in molecular biology, biotechnology and, nanotechnology. Many methods have been developed so far for the purification of these phages. However, it is important that phages retain their infecting properties, especially in biotechnological applications such as phage display technology. The most widely used is the PEG precipitation method, but it has some limitations such as impurities and reduced infectivity. To overcome them, we developed a new method for purification of M13 bacteriophages using syringe filters made of cellulose acetate membranes with a pore diameter of 0.22 µm. Phages were aggregated so that they could remain on the filters and for this purpose, the pH of the phage cultures was reduced to 3. The phage cultures were filtered and then the phages were recovered in tris-buffered saline (TBS) buffer (pH 10.5) by reversing the filter. The recovery rate was 250% higher than the standard PEG method. This new Faj-elek method offers an alternative to existing methods, allowing cheaper, easier and faster purification of M13 phages using syringe filters available in every research laboratory.

DOI: https://doi.org/10.1371/journal.pone.0325621
J Appl Microbiol. 2025 Jun 04. pii: lxaf136. [Epub ahead of print]

Environmental Phages: Ecosystem Dynamics, Biotechnological Applications and their limits, and Future Directions.

Bilel Hassen, Salah Hammami.

  Phages, the most abundant biological entities on Earth, play a crucial role in various microbial ecosystems, significantly impacting biogeochemical cycles and bacterial evolution. They inhabit diverse environments, including soil, water, and extreme conditions, where they contribute to the contribute to regulating microbial populations, facilitate genetic exchange and aid in nutrient cycling. Recent research has highlighted their potential in addressing antibiotic resistance, enhancing wastewater treatment, promoting agricultural sustainability, and tackling environmental issues. However, their ability to disseminate antibiotic resistance genes through horizontal gene transfer raises important concerns, warranting a thorough assessment of their ecological and biotechnological applications. This review synthesizes current knowledge on the diversity, ecological roles, and practical uses of environmental phages, emphasizing both their benefits and limitations. By analyzing recent findings and real-world applications, it provides insights into the challenges encountered and future directions for leveraging phages in environmental management, biotechnology, and healthcare.

Keywords:  antibiotic resistance; biocontrol; biogeochemical cycles; environmental phages; horizontal gene transfer; microbial ecology; phage applications; phages; phagotherapy; wastewater treatment

DOI:  https://doi.org/10.1093/jambio/lxaf136
J Antimicrob Chemother. 2025 May 31. pii: dkaf163. [Epub ahead of print]

Reversal of phenotypic resistance in multi-drug resistant carbapenemase-producing K. pneumoniae clinical isolates due to in vitro synergistic interactions between bacteriophages and antibiotics at clinically achievable concentrations.

Paschalis Paranos, Maria Siopi, Eleni Papanikolaou, Sophia Vourli, Panagoula Kolia, Spyros Pournaras, Joseph Meletiadis.

BACKGROUND: Therapeutic options for MDR carbapenemase-producing Klebsiella pneumoniae (CRKP) are limited. We therefore assessed the in vitro activity of five antibiotics from different classes in combination with lytic bacteriophages (phages) against MDR CRKP isolates.
MATERIAL AND METHODS: A total of 15 non-repetitive, well-characterized MDR CRKP isolates and four phages belonging to the Podoviridae family were used in chequerboard assays with amikacin, meropenem, ciprofloxacin, colistin and ceftazidime/avibactam. The spectrophotometrically determined MIC of drugs and phages alone and in combination were used to calculate the fractional inhibitory concentration index (FICi). The clinical relevance was assessed based on the MIC reductions at clinically achievable concentrations and below the corresponding susceptibility breakpoints. Emergence of resistance was studied in growth curves and time-kill experiments.
RESULTS: Synergy was found for ciprofloxacin in 6/15 (40%) isolates, meropenem in 10/15 (67%), ceftazidime/avibactam in 11/15 (73%), colistin in 8/15 (53%) and amikacin in 9/15 (60%) with all four phages against host bacteria. The synergistic interactions were strong as the FICi were 0.01-0.35 reducing the MICs (>90% growth inhibition) to clinically achievable concentrations for 87%-100% of strains, except ciprofloxacin. Reversal of phenotypic resistance was observed for amikacin, meropenem, colistin and ceftazidime/avibactam in 100%, 53%, 89% and 80% of isolates, respectively. No emergence of resistance was found for isolates with low level resistance to amikacin (MΙC 64 mg/L).
CONCLUSIONS: The phage-antibiotic combinations were synergistic against more than half of the isolates for all antibiotics except ciprofloxacin reversing resistance in most strains particularly with amikacin.

DOI: https://doi.org/10.1093/jac/dkaf163
PLoS One. 2025 ;20(6): e0325157

Resistance trend in bacteria isolated from corneal ulcers: A retrospective analysis from Pakistan.

Naila Obaid, Ayesha Saeed, Sidra Abbas, Shaghufta Perveen, Hajira Younas.

OBJECTIVE: The purpose of this study is to isolate and characterize bacteria from corneal ulcers and screen them for multiple antibiotic resistance, contributing to understanding patterns of resistance and identifying effective treatment strategies.
DESIGN: A retrospective study was conducted between January 2024 to August 2024.
SUBJECTS, PARTICIPANTS AND/OR CONTROLS: The study involved the isolation of pathogenic bacterial strains from 15 corneal ulcer samples.
METHODS, INTERVENTION, OR TESTING: We isolated and characterized bacterial strains from corneal ulcer samples, which were routinely collected at an ophthalmology clinic for suspected infectious corneal ulcers and examined their resistance to twenty-six routinely prescribed antibiotics. The bacterial species included methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and E. coli among others. Antibiotic resistance patterns were assessed, with a focus on commonly used antibiotics such as ciprofloxacin, gentamycin, and vancomycin.
MAIN OUTCOME MEASURES: The study measured the healing rates of corneal ulcer patients, antibiotic resistance levels across bacterial strains, and specific treatment responses to various antibiotics.
RESULTS: Thirteen out of fifteen corneal ulcer patients healed completely, while two patients developed full corneal opacity due to infection with P. aeruginosa. Significant differences in resistance were observed among the bacterial strains. MRSA exhibited the highest resistance levels, particularly to multiple antibiotics. Ciprofloxacin and gentamycin were less effective against the isolated strains, while vancomycin showed reduced resistance, against Gram-positive bacteria. Both ciprofloxacin and co-trimoxazole exhibited strong connections with multiple bacterial strains, indicating high resistance.
CONCLUSION: This study underscores the need for ongoing surveillance of antibiotic resistance patterns to guide treatment approaches and slow the spread of resistant bacteria. It also highlights the importance of developing new antibiotics and alternative therapies, with an emphasis on understanding the molecular mechanisms behind resistance to combat the global health posed by antibiotic-resistant infections.

DOI: https://doi.org/10.1371/journal.pone.0325157
Front Microbiol. 2025 ;16 1594533

Bacteriophage cocktail LEC2-LEC10 for broad-spectrum control of pathogenic and uncharacterized Escherichia coli in fresh produce.

Eo-Jin Kim, Sangryeol Ryu, Jeong-A Lim.

   Background: Escherichia coli is a major foodborne pathogen that causes intestinal diseases leading to severe illness. In particular, E. coli contamination in fresh produce presents a significant risk, because there are no additional sterilization processes before consumption. In this study, we characterized two novel bacteriophages, vB_EcoS_LEC2 and vB_EcoS_LEC10, and explored their use as a phage cocktail to control naturally occurring E. coli contamination in fresh foods.
Methods: Two phages were isolated, and their antimicrobial activity and target bacterial spectrum were analyzed. The efficacy of a two-phage cocktail was evaluated against E. coli O157:H7 strain mixtures and naturally occurring, unidentified E. coli present on commercially available vegetables. The bacterial receptors recognized by the phages were identified using receptor-deficient mutants. The genome sequences of the two phages were compared, focusing on receptor-binding protein genes.
Results: Characterizations revealed that both phages belonged to the Straboviridae family and were stable under various temperatures and pH conditions. The phages were confirmed to be strictly lytic, exhibiting short latent periods of 15 and 10 min and burst sizes of 22 and 189 phage particles per infected cell for LEC2 and LEC10, respectively. LEC2 and LEC10 exhibited distinct antimicrobial spectra, each with a broad but complementary host range among E. coli strains. Combining the two phages into a cocktail leveraged their complementary host specificities, broadening the overall host range and enhancing bacterial lysis against pathogenic E. coli mixtures compared to individual phages. The cocktail remarkably reduced the viability of naturally contaminated, unidentified E. coli in fresh vegetables, demonstrating its effectiveness in targeting diverse bacterial populations. LEC2 and LEC10 recognize different receptors, specifically lipopolysaccharide (LPS) (via WaaC) and OmpC, respectively, supporting their compatibility in a cocktail optimization. Furthermore, genome analysis confirmed the absence of lysogeny-related genes, toxins, and antibiotic resistance genes, reinforcing their suitability as safe biocontrol agents for food applications.
Conclusion: These results demonstrate that LEC2 and LEC10, especially when used as a cocktail, are promising antibacterial agents for controlling E. coli contamination in fresh foods. Their complementary host ranges and strong lytic activity support their application in food safety strategies aimed at reducing E. coli contamination.

Keywords:  Escherichia coli biocontrol; fresh food safety; genome characterization; lytic bacteriophages; phage cocktail; phage receptor analysis

DOI:  https://doi.org/10.3389/fmicb.2025.1594533
Invest Ophthalmol Vis Sci. 2025 Jun 02. 66(6): 15

Alterations of the Enteric Virome in Vogt-Koyanagi-Harada Disease.

Mingzhu Liu, Jiawei Geng, Siyan Jin, Ping Hu, Xia Wang, Xiaoli Liu.

Purpose: This study aims to explore the enteric virome characteristics of Vogt Koyanagi Harada (VKH) disease and its potential role in this disease.
Methods: Shotgun metagenomic sequencing was used to detect the enteric virome and 16S rRNA to detect the bacteriome in new-onset, untreated patients with VKH (n = 25) and age- and sex-matched healthy controls without autoimmune diseases (n = 25).
Results: Patients with VKH exhibited different enteric viral communities from healthy controls, characterized by decreased richness of core viral communities (present in > 80% of samples) and increased richness of common viral communities (present in 50%-80% of samples). Notably, within the core virus community, bacteriophage richness was markedly reduced, whereas eukaryotic virus richness significantly increased in patients with VKH. The case-control analysis identified 42 differentially abundant viruses, including a decrease in crAss-like phages, the eukaryotic virus Moumouvirus_moumou, and an enrichment of the Chlamydiamicrovirus_CPG1. Most of the differential phages predominantly targeted bacteria from the phyla Pseudomonadota and Firmicutes. The gut virome-bacteria community correlation analysis revealed a shift in the interactions between the core viruses and bacterial communities. Additionally, Wroclawvirus PA5oct (a Pseudomonas phage) correlated with leukotrichia, a clinically relevant symptom of VKH (P = 0.042). The impact of multiple Pseudomonas phages on the host folate biosynthesis was significantly enhanced in patients with VKH. Moreover, the protein (Earp361-372) encoded by VKH-enriched Pseudomonas was identified to share homology with the melanin antigen gp10044-59.
Conclusions: The gut virome of patients with VKH differs significantly from healthy controls, suggesting its disturbance may contribute to gut microbiome imbalance and VKH development.

DOI: https://doi.org/10.1167/iovs.66.6.15
Drug Dev Ind Pharm. 2025 Jun 06. 1-45

An Overview of Novel Formulations For Ocular Viral Infections: Focused On Nanomedicines.

Shalu Verma, Nidhi Nainwal, Divya Juyal.

  Ocular viral infections are a common cause of blindness globally. Many ocular viral infections are mistakenly identified as bacterial infections. In these situations, treatment is initiated belatedly and fails to address the root cause of the infection, which frequently results in serious ocular complications like corneal infiltrates, conjunctival scarring, and decreased visual acuity. The efficacy of conventional treatments for viral infections suffers from poor bioavailability, which requires the development of novel methods of drug delivery, accurate diagnosis, and efficient treatment choices. As nanotechnology in medicine advances at a rapid pace, multifunctional nanosystems are being prioritized more and more to address the problems brought on by viral infections of the eyes offering targeted delivery, increased bioavailability and decreased systemic toxicity. This study delivers a thorough overview of the use of nanomedicines in the treatment of ocular viral infections, with a particular emphasis on how they may enhance the safety and efficacy of antiviral drugs. We address a range of nanocarrier systems, such as liposomes, nanoparticles, nanosuspension, proniosomes, in-situ gels, dendrimers, and nanogels, emphasizing their distinct characteristics that facilitate the effective transportation of antiviral drugs to ocular tissues. This article also highlighted the regulatory barriers of ocular nanoformulation. The transition of in-vitro studies to in-vivo and clinical models has been discussed. This review also highlights the Preclinical studies of ocular viral treatment, ocular nanotoxicology and advancement of ocular antiviral treatments in the form of patents, ongoing clinical trials and marketed formulations.

Keywords:  Application; Nanomedicine; Ocular; Virus; bioassessment; toxicity

DOI:  https://doi.org/10.1080/03639045.2025.2515998
Comput Struct Biotechnol J. 2025 ;27 1827-1837

Deep learning-guided structural analysis of a novel bacteriophage KPP105 against multidrug-resistant Klebsiella pneumoniae.

Seyoung Ko, Jaehyung Kim, Jae-Hyun Cho, Youngju Kim, Donghyuk Kim.

  The increasing prevalence of multidrug-resistant bacteria, particularly Klebsiella species, poses a significant global health threat. Bacteriophages have emerged as promising alternatives due to their specificity and efficacy against bacterial targets. Characterizing phages, alongside analyzing their protein structures provide crucial insights into their host specificity, infection mechanisms, and potential applications. In this study, we isolated a novel bacteriophage, KPP105, and conducted comprehensive physiological, genomic, and structural analysis. Physiological assessments revealed that KPP105 maintains stable activity across a wide range of pHs and temperature conditions and exhibits host-specific infection properties. Genomic analysis classified KPP105 as a member of the Demerecviridae family and identified it as a lytic bacteriophage harboring a lytic cassette. Deep learning-based structural analysis of host-interacting proteins, including the receptor-binding protein (RBP) and endolysin derived from KPP105, was performed. Structural similarity analysis indicated that its RBP facilitates interactions with host receptors and exhibits unique sequence patterns distinguishing Klebsiella strains from other bacteria. Structure-based functional analysis provided comprehensive insights into cell wall degradation with various peptidoglycan fragments. In conclusion, this study reports the physiological, genomic, and structural characteristics of the novel lytic bacteriophage KPP105, offering valuable insights into its potential as an alternative agent against multidrug-resistant Klebsiella infections.

Keywords:  Bacteriophage; Genomic analysis; Klebsiella pneumoniae; Protein structure prediction; Structural analysis

DOI:  https://doi.org/10.1016/j.csbj.2025.04.032
bioRxiv. 2025 May 19. pii: 2025.05.19.654895. [Epub ahead of print]

Multiobjective learning and design of bacteriophage specificity.

Nathan Novy, Phil Huss, Sarah Evert, Philip A Romero, Srivatsan Raman.

To better understand and design proteins, it is crucial to consider the multifunctional landscapes on which all proteins exist. Proteins are often optimized for single functions during design and engineering, without considering the countless other functionalities that may contribute to or interfere with the intended outcome. In this work, we apply deep learning to understand and design the multifunctional host-targeting landscape of the T7 bacteriophage receptor binding protein for enhanced infectivity, pre-defined specificity, and high generality in virulence toward unseen strains. We compare several different model architectures and design approaches and experimentally characterize designed phages optimized for 26 diverse tasks. We demonstrate that with multiobjective machine learning, it is possible to design complex specificities at success rates that can enable low-throughput validation of predicted hits. Our results show that the targeting capabilities of T7 are highly plastic, with opposite specificities often separated by only a few mutations. This level of tunability underscores how models trained on multifunctional data can uncover key principles of phage biology and specificity. The same modeling framework can be applied to guide the multiobjective design of other proteins or mutable biological systems, offering a general strategy for navigating multifunctional landscapes.

DOI: https://doi.org/10.1101/2025.05.19.654895
J Pept Sci. 2025 Jul;31(7): e70034

Phage Display-Selected Peptides: Research and Clinical Applications in Cancer Imaging.

Atike Nur Cimen, Melis Hazal Porsuk, Ozlem Kutlu, Sibel Cetinel.

  Phage display has emerged as a groundbreaking technique for discovering novel biomolecules with significant applications in cancer diagnosis and therapy. This technique employs genetically engineered bacteriophages to display diverse libraries of peptides on their coat proteins, enabling the identification of candidates through a biopanning process targeting specific cancer markers. Biomolecules identified via phage display are widely used as molecular tools, often labeled with imaging agents or conjugated to nanoparticles for noninvasive tumor imaging. This review provides a comprehensive overview of recent advancements in phage display applications in cancer research over the past 5 years and prominent examples of clinical studies. The analysis underscores the potential of phage display to deliver diagnostic and therapeutic biomolecules, highlighting its promise for future clinical implementation in cancer imaging.

Keywords:  cancer; imaging; peptide; phage display

DOI:  https://doi.org/10.1002/psc.70034
Front Immunol. 2025 ;16 1567584

Peptide vaccines: an innovative therapeutic approach against antibiotic-resistant bacterial infections.

Fatemeh Tavassoli Razavi, Nasrin Salari, Atena Emami, Dariush Haghmorad, Rasoul Baharlou.

  Bacterial infections continue to pose a serious threat to global health, especially with the growing challenge of multidrug-resistant pathogens. While traditional vaccines have been pivotal in reducing disease burden, they come with limitations such as variable efficacy, safety concerns, and limited ability to address the diversity of bacterial strains. This review highlights the promise of peptide-based vaccines as an innovative approach to overcoming these hurdles. By targeting specific regions of bacterial proteins, peptide vaccines can elicit precise immune responses with improved safety and broader applicability. Advances in technology, including bioinformatics and delivery systems, have enhanced their design, making them more stable, effective, and easier to produce. These vaccines work by activating both antibody and T-cell responses through well-defined mechanisms. Different types, such as linear peptides, cyclic peptides, and synthetic long peptides, offer diverse strategies to tailor immune protection. The role of adjuvants and advanced delivery methods, like nanoparticles and liposomes, further improve their potential. Exciting progress has been made against the ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Peptide vaccines offer a forward-thinking, adaptable solution to reduce bacterial infections and mitigate the rise of antibiotic resistance, paving the way for safer and more effective prevention strategies. This review underscores the critical role of peptide-based vaccines in combating bacterial infections, advocating for ongoing research to unlock their full potential.

Keywords:  Acinetobacter baumannii; Enterobacter spp; Enterococcus faecium; Klebsiella pneumoniae; Pseudomonas aeruginosa; methicillin-resistant Staphylococcus aureus; peptide vaccines

DOI:  https://doi.org/10.3389/fimmu.2025.1567584
Gut Microbes. 2025 Dec;17(1): 2508426

Implications of gut microbiota-mediated epigenetic modifications in intestinal diseases.

Qihong Zhang, Yun Liu, Yuheng Li, Guangdong Bai, Jiaman Pang, Miaomiao Wu, Jiawei Li, Xuan Zhao, Yaoyao Xia.

  Intestinal diseases are highly prevalent, affecting millions worldwide and significantly contributing to global morbidity. The treatment of complex disorders, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), remains challenging due to multifactorial etiologies, diverse patient responses, and the limitations of current therapeutic strategies. Although the gut microbiota clearly plays a role in regulating the onset of intestinal diseases, few studies have explored the epigenetic factors by which the microbiota contributes to disease development. Here, the latest insights into the molecular mechanisms underlying the bidirectional influence between gut microbiota and epigenetic modifications are discussed, including DNA methylation, histone modifications, non-coding RNAs, and N6-methyladenosine (m6A). Importantly, mechanistic studies based on animal models or human cells have demonstrated that the gut microbiota, and other environmental factors, influence targeted gene expression and activate immune pathways through host epigenetic dysregulation, which are closely associated with the development of IBD and CRC. Furthermore, potential microbiome interventions, including probiotics, prebiotics and postbiotics, fecal microbiota transplantation (FMT), dietary modifications, and phage therapy, have been proposed as innovative therapeutic strategies to correct these abnormal epigenetic patterns associated with the diseases. Overall, addressing microbiome dysbiosis and its epigenetic consequences presents a promising frontier in the treatment of intestinal diseases, offering the potential to not only restore microbial balance but also provide more targeted and personalized therapeutic strategies for better patient outcomes.

Keywords:  Epigenetic modification; gut microbiota; intestinal disease; microbial intervention

DOI:  https://doi.org/10.1080/19490976.2025.2508426
Curr Rev Clin Exp Pharmacol. 2025 ;20(3): 207-228

Understanding Diabetic Wounds: A Review of Mechanisms, Pathophysiology, and Multimodal Management Strategies.

Manisha, Niharika, Praveen Gaur, Radha Goel, Kanak Lata, Rosaline Mishra.

   INTRODUCTION: Diabetic wounds are a prevalent and impairing consequence of diabetes mellitus that significantly impacts people's lives and global healthcare systems. Because of disturbances in the wound-healing cascade, these intricate, persistent wounds frequently refuse to heal. Focusing on diabetic wound formation, this study seeks to clarify the complex mechanisms and pathophysiology involved while offering a thorough overview of modern multimodal therapy techniques. The etiology of diabetic wounds entails a complex interplay between tissue destruction caused by hyperglycemia, neuropathy, ischemia, and compromised immune response. Extended inflammation, abnormal protease activity, and low oxygen levels in the tissue exacerbate the healing process. Comprehending these pathogenic mechanisms is essential for formulating efficacious therapeutic strategies.
METHODOLOGY: A thorough evaluation of the literature was done. Databases like SciFinder, ScienceDirect, PubMed, Google, Google Scholar, and the Egyptian Knowledge Bank were used to find pertinent publications. More than 200 articles and databases were studied to constitute this paper. The accuracy of the retrieved data was carefully reviewed and cross-checked. The current review aims to define wounds, various methods of classification, and various advancements for wound management. Several multidisciplinary strategies, including debridement, unloading, antimicrobial stewardship, and innovative therapeutics, are currently needed to manage diabetic wounds. Debridement-the excision of non-viable tissue-is necessary to create an environment that is conducive to recovery. Biomechanical interventions and offloading help to prevent additional tissue damage caused by repetitive stress. Antimicrobial treatments fight infections, which are a common diabetic wound consequence. Promising supplementary treatments are provided by developments in cellular and tissue-based products, ozone therapy growth factors, bioengineered skin substitutes, and hyperbaric oxygen therapy.
RESULTS: After applying article selection criteria and reviewing the quality of the methodology a total of 200 articles were selected to be included in the review. In this review, intricate interactions between peripheral neuropathy, vascular insufficiency, and hyperglycemia in the pathophysiology of diabetic wounds are explained. The efficacy of multimodal therapies is discussed in detail.
DISCUSSION: A thorough comprehension of the complex mechanisms that underlie diabetic wounds is essential for efficient therapy. This review emphasizes how important multimodal approaches are to treating the complex pathophysiology of these wounds. Clinicians can greatly enhance the prognosis of patients with diabetic foot ulcers by addressing vascular insufficiency, neuropathy, infection, and poor healing.
CONCLUSION: Timely wound resolution remains a key difficulty despite the implementation of multimodal methods. To customize therapies, personalized medicine strategies utilizing genetic and proteomic biomarkers must be the main focus of future research. Furthermore, cutting-edge biotechnologies with the potential to transform diabetic wound treatment include optogenetics and nanomedicine.

Keywords:  Diabetic wound; molecular mechanism; neuropathy; optogenetics.; wound care; wound healing

DOI:  https://doi.org/10.2174/0127724328326480240927065600