bims-fagtap 2025-06-01 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–06–01
25 papers selected by
Luca Bolliger, lxBio

Mini-review: Insight of bacteriophage therapy in clinical practice.
Bridging phage production models and practical applications to control antibiotic-resistant bacteria.
Virological and Pharmaceutical Properties of Clinically Relevant Phages.
Phage-induced protection against lethal bacterial reinfection.
Phage therapy: A novel approach to combat drug-resistant pathogens.
Klebsiella Lytic Phages Induce Pseudomonas aeruginosa PAO1 Biofilm Formation.
Bacteriophage therapy for critical antibiotic-resistant Gram-positive bacteria: A systematic review of clinical researches.
Pulsed Blue Light and Phage Therapy: A Novel Synergistic Bactericide.
Phage DisCo: targeted discovery of bacteriophages by co-culture.
Bacteriophages as Targeted Therapeutic Vehicles: Challenges and Opportunities.
Bactericidal synergism between phage and antibiotics: A combination strategy to target multidrug-resistant Klebsiella pneumoniae in vitro and in vivo.
Phage therapy in patients with urinary tract infections: a systematic review.
World Health Organisation's Bacterial Pathogen Priority List (BPPL) 2017 and BPPL 2024 to combat global antimicrobial resistance crisis: 'challenges and opportunities'.
Characterizations of Newly Isolated Erwinia amylovora Loessnervirus-like Bacteriophages from Hungary.
Genetic engineering of bacteriophage S16 for Salmonella separation, concentration, and detection.
Role of bestatin as a treatment for periodontitis.
Bacteriophage-Antibiotic Synergy Enhances Therapeutic Efficacy Against Multidrug-Resistant Klebsiella Pneumoniae Infections.
Isolation and Genomic Analysis of Escherichia coli Phage AUBRB02: Implications for Phage Therapy in Lebanon.
Pseudomonas aeruginosa: persistence beyond antibiotic resistance.
Cytokines Meet Phages: A Revolutionary Pathway to Modulating Immunity and Microbial Balance.
Novel treatments for bacterial keratitis: A review.
Accurate Diagnosis of Pseudomonas aeruginosa Is Critical to Mitigating Development of Antibiotic Resistance.
Biomedical Application of Nanogels: From Cancer to Wound Healing.
A group with emerging potential in the clinical and public health realms: the genus Providencia.
In Vitro Analysis of Interactions Between Staphylococcus aureus and Pseudomonas aeruginosa During Biofilm Formation.

Virology. 2025 May 20. pii: S0042-6822(25)00196-5. [Epub ahead of print]610 110583

Mini-review: Insight of bacteriophage therapy in clinical practice.

Smita Ghosh, Shrabani Pradhan, Kuntal Ghosh.

  The emergence of drug-resistant microorganisms requires implementing alternative therapy rather than antibiotics. Phage therapy is a fantastic substitute for antibiotics. Compared to antibiotics, phage therapy has many benefits, such as high specificity for the target bacteria, auto-dosing, biofilm penetration, and a decreased likelihood of resistance development. Regulatory issues, manufacturing barriers, the possibility of phage resistance, and interactions with the human immune system are only a few of the major obstacles that still exist. Various phage-derived enzymes and bioengineered phages may increase the therapeutic potential to combat antibiotic-resistant infections. This mini-review is compiled from research on phage mechanisms in mammalian immune systems, therapeutic uses, regulatory issues, and phage engineering advancements. Thus, it offers a hopeful future in phage therapy by offering a thorough overview of the therapeutic potentiality of phage and the global aspects of phage therapy. In conclusion, phages are expected to become an alternative treatment for antibiotics against multidrug-resistant (MDR) bacteria for medical purposes.

Keywords:  Antibiotic resistance; Phage therapy; Regulatory issues; Therapeutic potentiality

DOI:  https://doi.org/10.1016/j.virol.2025.110583
Microbiol Res. 2025 May 20. pii: S0944-5013(25)00186-7. [Epub ahead of print]298 128230

Bridging phage production models and practical applications to control antibiotic-resistant bacteria.

Xiaoyu Wang, Song Zhang, Juhee Ahn.

  The emergence of multidrug-resistant (MDR) bacteria represents a significant global health threat, demanding urgent development of alternative treatment strategies. Bacteriophages (phages) have gained attention as promising alternatives to antibiotics due to their specificity, abundance, and minimal side effects, leading to potential applications in food safety, agriculture, aquaculture, and clinical settings. However, the practical use of phage therapy is limited by challenges in efficiently producing phages, due to the complex and dynamic interactions between bacteria and phages. Therefore, this review aims to bridge the gap between theoretical models and practical applications by examining bacteria-phage interactions, focusing on the coevolution of bacteria and phages, their resistance mechanisms, and the environmental factors that influence these interactions. Differential and stochastic mathematical models were used to analyze essential kinetic parameters in phage production and to assess strategies for optimizing phage production and their application in controlling antibiotic-resistant infections. Additionally, mathematical modeling in phage-bacteria dynamics was provided, highlighting new kinetic models that incorporated the evolutionary trade-offs between antibiotic resistance and phage resistance. These models provide valuable insights into the factors that influence bacteria-phage interactions and assist in designing effective treatment strategies to optimize the clinical use of phages by predicting phage behavior and therapeutic effects. Therefore, mathematical modeling serves as an invaluable tool in advancing phage therapy. Further study is needed to increase phage production and improve therapy consistency for establishing phage therapy as a reliable solution for multidrug-resistant infections.

Keywords:  Antibiotic resistance; Bacteria-phage interactions; Evolutionary trade-offs; Kinetic models; Mathematical modeling; Phage therapy

DOI:  https://doi.org/10.1016/j.micres.2025.128230
Antibiotics (Basel). 2025 May 10. pii: 487. [Epub ahead of print]14(5):

Virological and Pharmaceutical Properties of Clinically Relevant Phages.

Antonios-Periklis Panagiotopoulos, Antonia P Sagona, Deny Tsakri, Stefanos Ferous, Cleo Anastassopoulou, Athanasios Tsakris.

  As antimicrobial resistance continues to undermine the efficacy of antibiotics, the global medical community is increasingly turning to alternative treatment modalities. Among these, phage therapy has re-emerged as a promising strategy for managing multidrug-resistant bacterial infections. Herein, we present and briefly discuss eight essential attributes of clinically relevant phages for therapy, which may be categorized broadly into virological and pharmacological characteristics. Virological attributes include a broad host range, a strictly lytic life cycle and the ability to manage the emergence of bacterial resistance to phages. Comprehensive genomic and proteomic characterization forms the foundation for selecting and engineering such candidates, ensuring both safety and predictability. From a pharmacological standpoint, phages should ideally show safety across relevant formulations and routes of administration, favorable pharmacokinetics, stability during storage and scalability in manufacturing. Advances in genomic analysis, artificial intelligence-driven phage selection and formulation technologies have further accelerated the translational potential of phage therapy. By systematically addressing each of these critical attributes, this work aims to inform the rational selection and development of therapeutic phages suitable for integration into the clinical practice.

Keywords:  antimicrobial resistance; genomic and proteomic characterization; lytic bacteriophages; phage therapy; pharmacokinetics

DOI:  https://doi.org/10.3390/antibiotics14050487
Proc Natl Acad Sci U S A. 2025 Jun 03. 122(22): e2423286122

Phage-induced protection against lethal bacterial reinfection.

Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso.

  Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, providing almost complete protection against a second lethal infection for animals treated with phage therapy. The activity also reduced infection burden an astounding billion-fold over the control. Reinfection protection requires phage lytic killing of its target bacterium but is independent of additional phage therapy. The effect is not driven by phage alone, lingering phage resistors, or a sublethal inoculum. In vitro phage-lysed bacteria provide partial protection, suggesting a combination of phage-induced lytic activity and immune stimulation by phage treatment is responsible for the effect. These observations imply certain phages may induce host adaptive responses following the lysis of the infecting bacteria. This work suggests phage therapy may contain a dual-action effect, an initial treatment efficacy followed by a long-term protection against reoccurring infection, a therapeutic-vaccination mechanism of action.

Keywords:  ExPEC; immunity; phage therapy; sepsis

DOI:  https://doi.org/10.1073/pnas.2423286122
Microbiol Res. 2025 May 21. pii: S0944-5013(25)00184-3. [Epub ahead of print]298 128228

Phage therapy: A novel approach to combat drug-resistant pathogens.

Mengru Yao, Yuan Zhu, Jin-Ao Duan, Ping Xiao.

  Antibiotic-resistant infections, such as those caused by the overuse of antibiotics, have greatly strained healthcare systems. Among them, drug-resistant bacteria ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are typical and common. Enterococcus faecalis and Escherichia coli are of equal concern. These pathogens often have higher pathogenicity than the same strains, and resistance has reduced treatment options, so new treatment options are needed to address these pathogens. This review analyzes recent studies related to phage therapy for the treatment of bacterial infections in various parts of the human body (e.g., alcoholic liver disease, skin, and soft tissues, respiratory tract, gastrointestinal tract, urinary system, etc.), to better understand the potential role of phage therapy as a non-antibiotic strategy for the treatment of infections caused by drug-resistant bacteria. In addition, this review introduces a series of products related to phage therapy and points out potential research directions for phage therapy in clinical applications. This paper elucidates the basic mechanism of human infection by some drug-resistant bacteria and the therapeutic effect of phage therapy against drug-resistant bacteria. It popularizes the understanding of phage therapy and provides a reference for research on its use for drug-resistant bacterial infections.

Keywords:  Antimicrobial resistance; Bacterial infection; Bacteriophage; ESKAPE; Phage product; Phage therapy

DOI:  https://doi.org/10.1016/j.micres.2025.128228
Viruses. 2025 Apr 25. pii: 615. [Epub ahead of print]17(5):

Klebsiella Lytic Phages Induce Pseudomonas aeruginosa PAO1 Biofilm Formation.

Grzegorz Guła, Grazyna Majkowska-Skrobek, Anna Misterkiewicz, Weronika Salwińska, Tomasz Piasecki, Zuzanna Drulis-Kawa.

  Bacterial biofilms, characterized by complex structures, molecular communication, adaptability to environmental changes, insensitivity to chemicals, and immune response, pose a big problem both in clinics and in everyday life. The increasing bacterial resistance to antibiotics also led to the exploration of lytic bacteriophages as alternatives. Nevertheless, bacteria have co-evolved with phages, developing effective antiviral strategies, notably modification or masking phage receptors as the first line of defense mechanism. This study investigates viral-host interactions between non-host-specific phages and Pseudomonas aeruginosa, assessing whether bacteria can detect phage particles and initiate protective mechanisms. Using real-time biofilm monitoring via impedance and optical density techniques, we monitored the phage effects on biofilm and planktonic populations. Three Klebsiella phages, Slopekvirus KP15, Drulisvirus KP34, and Webervirus KP36, were tested against the P. aeruginosa PAO1 population, as well as Pseudomonas Pbunavirus KTN6. The results indicated that Klebsiella phages (non-specific to P. aeruginosa), particularly podovirus KP34, accelerated biofilm formation without affecting planktonic cultures. Our hypothesis suggests that bacteria sense phage virions, regardless of specificity, triggering biofilm matrix formation to block potential phage adsorption and infection. Nevertheless, further research is needed to understand the ecological and evolutionary dynamics between phages and bacteria, which is crucial for developing novel antibiofilm therapies.

Keywords:  Klebsiella phages; Pseudomonas aeruginosa; biofilm; non-specific viral–bacteria interactions

DOI:  https://doi.org/10.3390/v17050615
Microbiol Res. 2025 May 22. pii: S0944-5013(25)00187-9. [Epub ahead of print]298 128231

Bacteriophage therapy for critical antibiotic-resistant Gram-positive bacteria: A systematic review of clinical researches.

Xinyu Nie, Yigang Tong, Mengzhe Li, Zhenbo Ning, Huahao Fan.

  The emergence of antibiotic-resistant bacteria compromises medical interventions and poses a significant threat to global public health systems. Bacteriophage (phage) therapy offers a promising, natural, safe, and effective antimicrobial alternative, particularly advantageous for combating Gram-positive bacteria with increasing resistance. This systematic review synthesizes clinical cases published in recent 15 years, evaluating the safety and efficacy of phage therapy in treating Gram-positive bacterial infections. It details the mechanisms of action and applications of phages in treating Gram-positive bacterial infections, critically assessing phage cocktail, phage-assisted regimens, and phage-derived agents. The review further studies phage's interaction with human host, commensal microbiota, and immune system. Through the rigorous analysis, it identifies phage therapy's potential implementation obstacles, and provides valuable perspectives for future research and clinical treatment.

Keywords:  Bacteriophage therapy; Clinical treatment; Multidrug-resistant Gram-positive bacteria; Systematic review

DOI:  https://doi.org/10.1016/j.micres.2025.128231
Antibiotics (Basel). 2025 May 09. pii: 481. [Epub ahead of print]14(5):

Pulsed Blue Light and Phage Therapy: A Novel Synergistic Bactericide.

Amit Rimon, Jonathan Belin, Ortal Yerushalmy, Yonatan Eavri, Anatoly Shapochnikov, Shunit Coppenhagen-Glazer, Ronen Hazan, Lilach Gavish.

  Background: Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) strains are an increasing cause of morbidity and mortality. Pulsed blue light (PBL) enhances porphyrin-induced reactive oxygen species and has been clinically shown to be harmless to the skin at low doses. Bacteriophages, viruses that infect bacteria, offer a promising non-antibiotic bactericidal approach. This study investigates the potential synergism between low-dose PBL and phage therapy against P. aeruginosa in planktonic cultures and preformed biofilms. Methods: We conducted a factorial dose-response in vitro study combining P. aeruginosa-specific phages with PBL (457 nm, 33 kHz) on both PA14 and multidrug-resistant PATZ2 strains. After excluding direct PBL effects on phage titer or activity, we assessed effectiveness on planktonic cultures using growth curve analysis (via growth_curve_outcomes, a newly developed, Python-based tool available on GitHub) , CFU, and PFU. Biofilm efficacy was evaluated using CFU post-sonication, crystal violet staining, and live/dead staining with confocal microscopy. Finally, we assessed reactive oxygen species (ROS) as a potential mechanism using the nitro blue tetrazolium reduction assay. ANOVA or Kruskal-Wallis tests with post hoc Tukey or Conover-Iman tests were used for comparisons (n = 5 biological replicates and technical triplicates). Results: The bacterial growth lag phase was significantly extended for phage alone or PBL alone, with a synergistic effect of up to 144% (p < 0.001 for all), achieving a 9 log CFU/mL reduction at 24 h (p < 0.001). In preformed biofilms, synergistic combinations significantly reduced biofilm biomass and bacterial viability (% Live, median (IQR): Control 80%; Phage 40%; PBL 25%; PBL&Phage 15%, p < 0.001). Mechanistically, PBL triggered transient ROS in planktonic cultures, amplified by phage co-treatment, while a biphasic ROS pattern in biofilms reflected time-dependent synergy. Conclusions: Phage therapy combined with PBL demonstrates a synergistic bactericidal effect against P. aeruginosa in both planktonic cultures and biofilms. Given the strong safety profile of PBL and phages, this approach may lead to a novel, antibiotic-complementary, safe treatment modality for patients suffering from difficult-to-treat antibiotic-resistant infections and biofilm-associated infections.

Keywords:  Pseudomonas; bacteriophage; biofilm; blue light; phage therapy; photobiomodulation

DOI:  https://doi.org/10.3390/antibiotics14050481
mSystems. 2025 May 28. e0164424

Phage DisCo: targeted discovery of bacteriophages by co-culture.

Eleanor A Rand, Natalia Quinones-Olvera, Kesther D C Jean, Carmen Hernandez-Perez, Siân V Owen, Michael Baym.

  Phages interact with many components of bacterial physiology from the surface to the cytoplasm. Although there are methods to determine the receptors and intracellular systems a specified phage interacts with retroactively, finding a phage that interacts with a chosen piece of bacterial physiology a priori is very challenging. Variation in phage plaque morphology does not to reliably distinguish distinct phages, and therefore many potentially redundant phages may need to be isolated, purified, and individually characterized to find phages of interest. Here, we present a method in which multiple bacterial strains are co-cultured on the same screening plate to add an extra dimension to plaque morphology data. In this method, phage discovery by co-culture (Phage DisCo), strains are isogenic except for fluorescent tags and one perturbation expected to impact phage infection. Differential plaquing on the strains is easily detectable by fluorescent signal and implies that the perturbation made to the surviving strain in a plaque prevents phage infection. We validate the Phage DisCo method by showing that characterized phages have the expected plaque morphology on Phage DisCo plates and demonstrate the power of Phage DisCo for multiple targeted discovery applications, from receptors to phage defense systems.IMPORTANCEIn this work, we describe a targeted phage discovery method that allows immediate isolation of phages with specific traits. Currently, to find a phage with specific properties, huge libraries of phages must be collected and screened retroactively. This assay, Phage Discovery by Co-culture (Phage DisCo), works by co-culture of host strains that are identical except for one perturbation that may interfere with phage infection and a unique fluorescent marker. These strains are co-cultured with an environmental sample of interest in traditional plaque assay format, making phage characteristics easily identifiable by fluorescent signal after imaging of the screening plate. We validate that Phage DisCo can identify phages with specific properties, even when these phages are rare in samples. This approach allows rapid exploration of the diversity within phage samples with vastly streamlined processes, and we anticipate it will be widely adopted within the phage discovery field.

Keywords:  bacteriophage therapy; bacteriophages; phage defense; phage receptor

DOI:  https://doi.org/10.1128/msystems.01644-24
Bioengineering (Basel). 2025 Apr 29. pii: 469. [Epub ahead of print]12(5):

Bacteriophages as Targeted Therapeutic Vehicles: Challenges and Opportunities.

Srividhya Venkataraman, Mehdi Shahgolzari, Afagh Yavari, Kathleen Hefferon.

  Bacteriophages, with their distinctive ability to selectively target host bacteria, stand out as a compelling tool in the realm of drug and gene delivery. Their assembly from proteins and nucleic acids, coupled with their modifiable and biologically unique properties, enables them to serve as efficient and safe delivery systems. Unlike conventional nanocarriers, which face limitations such as non-specific targeting, cytotoxicity, and reduced transfection efficiency in vivo, engineered phages exhibit promising potential to overcome these hurdles and improve delivery outcomes. This review highlights the potential of bacteriophage-based systems as innovative and efficient systems for delivering therapeutic agents. It explores strategies for engineering bacteriophage, categorizes the principal types of phages employed for drug and gene delivery, and evaluates their applications in disease therapy. It provides intriguing details of the use of natural and engineered phages in the therapy of diseases such as cancer, bacterial and viral infections, veterinary diseases, and neurological disorders, as well as the use of phage display technology in generating monoclonal antibodies against various human diseases. Additionally, the use of CRISPR-Cas9 technology in generating genetically engineered phages is elucidated. Furthermore, it provides a critical analysis of the challenges and limitations associated with phage-based delivery systems, offering insights for overcoming these obstacles. By showcasing the advancements in phage engineering and their integration into nanotechnology, this study underscores the potential of bacteriophage-based delivery systems to revolutionize therapeutic approaches and inspire future innovations in medicine.

Keywords:  Alzhiemer’s disease; CRISPR-Cas9 system; cancer; infectious diseases; mAbs; phage display; phage therapy; theranostics

DOI:  https://doi.org/10.3390/bioengineering12050469
Eur J Pharm Biopharm. 2025 May 28. pii: S0939-6411(25)00136-5. [Epub ahead of print] 114759

Bactericidal synergism between phage and antibiotics: A combination strategy to target multidrug-resistant Klebsiella pneumoniae in vitro and in vivo.

Shuxian Wang, Wenqi Fan, Rulin Jin, Weiqing Lan, Yong Zhao, Xiaohong Sun.

  Bacteriophages have reemerged to potentially replace or complement the role of antibiotics, as bacterial viruses have the ability to inactivate pathogens. However, certain intrinsic limitations of phages overshadow their clinical application, particularly their narrow host spectrum and rapid development of resistance upon treatment. This study aimed to explore the synergistic antimicrobial effect of phage combined with antibiotics against Klebsiella pneumoniae. The time-killing experiments in vitro showed that phage and gentamicin combination displayed synergistic bactericidal activity, leading to a reduction in the minimum inhibitory concentration of gentamicin. Furthermore, the phage HS106/gentamicin combination significantly inhibited biofilm formation and eliminated mature biofilms. On the other hand, phage treatment for 2 h before gentamicin treatment produced better synergistic inhibitory effect. The use of phage followed by gentamicin can effectively inhibit the efflux effect. Surprisingly, the phage HS106/gentamicin combination still exhibited antimicrobial activity against phage-resistant mutants and double-resistant mutants. Finally, the phage HS106/gentamicin combination significantly increased the survival rate of zebrafish infected with K. pneumoniae, indicating its excellent bactericidal activity in vivo. Overall, the phage HS106/gentamicin combination may provide a promising approach for treating infections caused by high-level multidrug-resistant K. pneumoniae.

Keywords:  Biofilms inhibition; Multidrug-resistant Klebsiella pneumoniae; Phage resistance; Phage-antibiotic synergy; Zebrafish

DOI:  https://doi.org/10.1016/j.ejpb.2025.114759
Expert Rev Anti Infect Ther. 2025 May 28.

Phage therapy in patients with urinary tract infections: a systematic review.

Romaric Larcher, Aurélien Dinh, Boris Monnin, Paul Laffont-Lozes, Paul Loubet, Jean-Philippe Lavigne, Franck Bruyere, Albert Sotto.

   INTRODUCTION: Urinarytract infections (UTIs) caused by multidrug-resistant (MDR) andextensively drug-resistant (XDR) bacteria are challenging to treat.This systematic review evaluates bacteriophage therapy as analternative or adjunct to antibiotics for UTIs.
RESEARCHDESIGN AND METHODS: Acomprehensive search was conducted in PubMed, Embase, Web of Science,and Cochrane databases. Studies reporting bacteriophage therapy inUTIs, with outcomes related to safety and efficacy, were included.Studies unrelated to UTIs or lacking clear outcomes were excluded.Bias was assessed using RoB2 and JBI appraisal tools for series andcase reports. Data were synthesized narratively due to studyheterogeneity.
RESULTS: From576 articles screened, 12 studies met the inclusion criteria,comprising 89 participants, many with MDR and XDR infections. Phagetherapy was generally well-tolerated, with few adverse effects.Efficacy varied, with some studies showing complete infectionresolution, particularly in high-risk patients, while others reportedpartial or no improvement. Phage therapy often served as the soleviable treatment for XDR infections, yielding positive resultsdespite small sample sizes and data heterogeneity.
CONCLUSIONS: Phagetherapy shows promise for treating UTIs, especially those withlimited treatment options, but uncertainties remain regarding dosingand administration. Further randomized trials are needed to confirmits efficacy and safety.
PROTOCOLREGISTRATION: www.crd.york.ac.uk/prospero identifier isCRD42023431617.

Keywords:  Bacteriophage; Cystitis; Phage; Prostatitis; Pyelonephritis; UTI; kidney transplant recipients; recurrent UTI, urinary tract infection

DOI:  https://doi.org/10.1080/14787210.2025.2513459
J Antimicrob Chemother. 2025 May 27. pii: dkaf167. [Epub ahead of print]

World Health Organisation's Bacterial Pathogen Priority List (BPPL) 2017 and BPPL 2024 to combat global antimicrobial resistance crisis: 'challenges and opportunities'.

Vazhayil Hari Krishnaprasad, Vijayashree Nayak, Sanjay Kumar.

Antibiotic resistance, in a broader perspective, antimicrobial resistance (AMR) presents a formidable global health challenge, threatening the effectiveness of antibiotics and other antimicrobial agents. As a result, AMR has become more challenging or even impossible to treat, leading to increased morbidity and mortality. The World Health Organisation (WHO) has been at the forefront of international efforts to combat AMR by sensitizing the world about the pressing need to tackle AMR to save the future of the human race. This article analyses WHO's efforts to combat AMR, including creating the Bacterial Pathogen Priority List (BPPL), developing a global action plan to address AMR and promoting surveillance and stewardship programmes. This article also examines the progress achieved by BPPL 2017 and the challenges ahead for BPPL 2024. Additionally, this article explores various efforts to combat AMR through two major approaches, like 'research and development' and 'the policy and regulation-based' approach. This article underscores various emerging strategies to tackle AMR, for example, biofilm disruption, nanotechnology, antibiotic resistance breakers, antibody-antibiotic conjugates, rapid detection tools and alternative therapies like phage therapy, antimicrobial peptides, CRISPR-Cas system, probiotics and microbiota modulations. This article also highlights the importance of coordinated actions and sustained commitment to safeguarding public health and ensuring the continued effectiveness of antimicrobial therapies.

DOI: https://doi.org/10.1093/jac/dkaf167
Viruses. 2025 May 06. pii: 677. [Epub ahead of print]17(5):

Characterizations of Newly Isolated Erwinia amylovora Loessnervirus-like Bacteriophages from Hungary.

Elene Lomadze, György Schneider, Szilvia Papp, Dominika Bali, Roberta Princz-Tóth, Tamás Kovács.

  This study explores alternative methods to combat bacterial infections like fire blight caused by Erwinia amylovora (Ea) using bacteriophages as potential antimicrobial agents. Two lytic phages, Ea PF 7 and Ea PF 9, were isolated from apple samples and classified as Loessnervirus-like based on their genomes. Both phages showed strong efficacy, lysing 95% of the tested 37 Ea strains. They inhibited bacterial growth for up to 10 h, even at low infection rates. The phages had a short latent period of 10 min and produced high burst sizes of 108 and 125 phage particles per infected cell. Stability tests revealed that both phages were stable at moderate temperatures (37-45 °C) and within a pH range of 4-10. However, their viability decreased at higher temperatures and extreme pH levels. Both phages exhibited notable desiccation tolerance and moderate resistance to UV-B radiation during UV testing. The phages were exposed to carefully controlled irradiation, considering factors like lamp type, radiation intensity, exposure time, and object distance. This method introduces a complex approach to research, ensuring repeatable and comparable results. These findings suggest that Ea PF 7 and Ea PF 9 hold promise as antimicrobial agents for therapeutic and biotechnological applications, potentially helping to combat antibiotic resistance in the future.

Keywords:  Erwinia amylovora; bacteriophage-based biocontrol; environmental stability; fire blight

DOI:  https://doi.org/10.3390/v17050677
Anal Bioanal Chem. 2025 May 27.

Genetic engineering of bacteriophage S16 for Salmonella separation, concentration, and detection.

Ranee K Anderson, Sam R Nugen.

  Salmonella contamination in food and water poses a major global health risk, creating an urgent need for rapid, reliable, and cost-effective detection methods. Conventional approaches are often expensive, labor-intensive, and time-consuming, and they frequently yield inconclusive or presumptive positive results. A significant bottleneck to rapid detection is the need to separate the target bacteria into smaller, clean, and concentrated samples. Bacteriophages can recognize, bind, and infect specific bacterial hosts. This study presents a genetically engineered S16 Salmonella-specific bacteriophage as a biosensor, optimized for enhanced sensitivity and efficiency in detecting Salmonella. Using CRISPR-Cas12a, the phages were engineered to include a gene for a NanoLuc luciferase reporter and a monomeric streptavidin (mSA) affinity tag fused to the gene for the capsid protein Soc. This design enabled conjugation of the phages to magnetic nanoparticles, facilitating the capture, concentration, and detection of Salmonella from 10 mL water samples. The modified S16 phage exhibited a detection limit of fewer than 10 CFU of Salmonella in 10 mL of water within a typical work shift. This innovative phage-based detection method offers a promising tool for enhancing food and water safety by providing a faster, more sensitive, and cost-effective approach to pathogen monitoring of Salmonella enterica subsp. enterica serovar Typhimurium.

Keywords:   Salmonella ; Bacteriophage; Biosensor; Food safety; Genetic engineering; Water safety

DOI:  https://doi.org/10.1007/s00216-025-05924-x
Front Dent Med. 2025 ;6 1571989

Role of bestatin as a treatment for periodontitis.

Sudhir Rama Varma, Bader Mohamed Moustafa Elagha, Jayaraj K Narayanan, Asok Mathew.

  Periodontitis is a chronic inflammatory disease impacting the supporting structures of teeth, with significant global pervasiveness and systemic health implications. Current treatments, such as scaling and root planning (SRP) and adjunctive antibiotics, face challenges including antibiotic resistance, infection recurrence, and incomplete tissue regeneration. Bestatin, a dipeptide aminopeptidase inhibitor, has shown potential as a novel therapeutic agent due to its targeted antimicrobial effects against Porphyromonas gingivalis (P. gingivalis), biofilm modulation, and anti-inflammatory properties. in vitro studies revealed bestatin's selective bacteriostatic effects against P. gingivalis, inhibiting bacterial growth and biofilm development without affecting commensal bacteria. in vivo studies demonstrated that bestatin modulated inflammatory responses and prevented necrotic abscess formation in guinea pig models, suggesting its potential to suppress P. gingivalis growth through alternative pathways. However, no clinical trials were identified, highlighting a significant gap in the translation of preclinical findings into human periodontal therapy. The current review highlights Bestatin as a promising therapeutic representative for periodontitis, where it is involved in inhibiting modulating biofilms, reducing tissue destruction, and P. gingivalis, in preclinical studies. Compared to traditional therapies, bestatin provides unique advantages, non-cytotoxicity, including specificity, and dual action against microbial dysbiosis along with biofilm-associated resistance.

Keywords:  Porphyromonas gingivalis; aminopeptidase inhibitor; antimicrobial therapy; bestatin; biofilm; periodontitis

DOI:  https://doi.org/10.3389/fdmed.2025.1571989
J Appl Microbiol. 2025 May 29. pii: lxaf131. [Epub ahead of print]

Bacteriophage-Antibiotic Synergy Enhances Therapeutic Efficacy Against Multidrug-Resistant Klebsiella Pneumoniae Infections.

Eman M Rabie Shehab El-Din, Bishoy Maher Zaki, Abeer M Abd El-Aziz, Youssif M Ali.

   AIMS: This study aims to evaluate the therapeutic efficacy of bacteriophage therapy alone or in combination with antibiotics in the treatment of acute infection caused by multidrug-resistant (MDR) Klebsiella pneumoniae.
METHODS AND RESULTS: In this study, we isolated and characterized a lytic bacteriophage vB_Kpn_FOPMU1, which exhibits potent antibacterial activity against K. pneumoniae. Whole-genome sequencing identified vB_Kpn_FOPMU1 as a member of the Przondovirus genus and revealed the presence of key lysis-associated genes, including those encoding endolysin, holin, and Rz-like spanin proteins. In vitro work demonstrated that incubation of bacteriophage and cefotaxime with K. pneumoniae significantly decreased the MIC of cefotaxime from 128µg mL-1 to 1 µg mL-1, indicating strong synergistic activity. Using a murine model of acute K. pneumoniae lung infection, we further demonstrated that the combination therapy significantly enhanced bacterial clearance compared to phage monotherapy. This synergistic approach restored sensitivity of K. pneumoniae to cefotaxime, prevented the emergence of phage-resistant bacterial mutants, and achieved superior bacterial eradication from both the lung and blood. Moreover, administration of the phage-antibiotic combination resulted in complete protection of infected mice, with a 100% survival rate, compared to a 60% survival rate observed in animals that received phage monotherapy. Therapeutic application of the bacteriophage-cefotaxime combination resulted in significantly improved lung pathology, characterized by reduced inflammatory cell infiltration and diminished tissue damage, compared to bacteriophage monotherapy.
CONCLUSION: Our findings underscore the potential of bacteriophage-antibiotic synergy as a promising therapeutic strategy to combat MDR K. pneumoniae infections and mitigate the risk of phage resistance development.

Keywords:   Klebsiella pneumoniae ; antibiotic resistance; bacteriophage therapy; lung infection model; multidrug-resistant; phage-antibiotic combination; synergistic effect

DOI:  https://doi.org/10.1093/jambio/lxaf131
Antibiotics (Basel). 2025 Apr 30. pii: 458. [Epub ahead of print]14(5):

Isolation and Genomic Analysis of Escherichia coli Phage AUBRB02: Implications for Phage Therapy in Lebanon.

Tasnime A Abdo Ahmad, Samar A El Houjeiry, Antoine Abou Fayad, Souha S Kanj, Ghassan M Matar, Esber S Saba.

   BACKGROUND/OBJECTIVES: Escherichia coli (E. coli), a prevalent Gram-negative bacterium, is a frequent cause of illness. The extensive use of antibiotics has led to the emergence of resistant strains, complicating antimicrobial therapy and emphasizing the need for natural alternatives such as phages.
METHODS: In this study, a novel Escherichia coli phage, AUBRB02, was isolated from sewage and characterized through whole-genome sequencing, host range assays, and biofilm elimination assays. The phage's stability and infectivity were assessed under various pH and temperature conditions, and different E. coli strains.
RESULTS: Phage AUBRB02 has an incubation period of 45 min, a lysis period of 10 min, and a burst size of 30 phages/infected cell. It is stable across pH 5.0-9.0 and temperatures from 4 °C to 60 °C. Treatment with AUBRB02 significantly reduced post-formation E. coli biofilms, as indicated by lower OD values compared with the positive control. The whole genome sequencing revealed a genome size of 166,871 base pairs with a G + C (Guanine and Cytosine content) content of 35.47%. AUBRB02 belongs to the Tequatrovirus genus, sharing 93% intergenomic similarity with its closest RefSeq relative, and encodes 262 coding sequences, including 10 tRNAs.
CONCLUSIONS: AUBRB02 demonstrates high infectivity and stability under diverse conditions. Its genomic features and similarity to related phages highlight its potential for phage therapy, offering promising prospects for the targeted treatment of E. coli infections.

Keywords:  Escherichia coli; antibacterial resistance; biofilm; lytic; phage

DOI:  https://doi.org/10.3390/antibiotics14050458
Trends Microbiol. 2025 May 28. pii: S0966-842X(25)00151-9. [Epub ahead of print]

Pseudomonas aeruginosa: persistence beyond antibiotic resistance.

Ruggero La Rosa, Søren Molin, Helle Krogh Johansen.

  The persistence of Pseudomonas aeruginosa in chronic infections extends beyond the issue of antibiotic resistance. A critical, yet unresolved question is why antibiotics fail to eradicate all infecting bacteria, despite P. aeruginosa often being phenotypically susceptible. This highlights the need for a comprehensive understanding of persistence mechanisms, which we consider to be directly rooted in host-pathogen interactions and which are frequently overlooked. We propose that both gene regulatory adaptation and adaptive genetic evolution play fundamental roles in the long-term persistence of P. aeruginosa. Elucidating these complex interactions has profound clinical implications, but their elucidation depends on access to advanced and innovative model systems that accurately replicate host-pathogen relationships.

Keywords:  antibiotic resistance; bacterial infection; host–pathogen interactions; infection models; metabolism; microbial persistence

DOI:  https://doi.org/10.1016/j.tim.2025.05.004
Biomedicines. 2025 May 15. pii: 1202. [Epub ahead of print]13(5):

Cytokines Meet Phages: A Revolutionary Pathway to Modulating Immunity and Microbial Balance.

Rossella Cianci, Mario Caldarelli, Paola Brani, Annalisa Bosi, Alessandra Ponti, Cristina Giaroni, Andreina Baj.

  Bacteriophages are a unique and fascinating group of viruses, known for their highly specific ability to infect and replicate within bacterial cells. While their potential as antibacterial agents has been recognized for decades, recent research has revealed complex interactions between phages and the human immune system, offering new insights into their role in immune modulation. New evidence reveals a dynamic and intricate relationship between phages and cytokines, suggesting their ability to regulate inflammation, immune tolerance, and host-pathogen interaction. Herein, we review how phages affect the production of cytokines and the behavior of immune cells indirectly by lysis of bacterium or directly on mammalian cells. Phages have been shown to induce both pro- and anti-inflammatory responses and recently, they have been explored in personalized immunotherapy, cancer immunotherapy, and microbiome modulation, which are the focus of this review. Several challenges remain despite significant progress, including practical obstructions related to endotoxins along with host microbiome variability and regulatory issues. Nevertheless, the potential of bacteriophages to modulate immune responses makes them attractive candidates for the future of precision medicine.

Keywords:  bacteriophage; cancer; cytokines; gut microbiota; immune system

DOI:  https://doi.org/10.3390/biomedicines13051202
Int J Pharm. 2025 May 28. pii: S0378-5173(25)00630-1. [Epub ahead of print] 125793

Novel treatments for bacterial keratitis: A review.

Chuan Yan, Hao Zhao, Qianhui Pan, Xinru Xie, Keyin Chen, Lishu Zhang.

  Bacterial keratitis (BK) is a critical ophthalmic emergency and one of the leading causes of corneal blindness. The current clinical management for BK involves surgical intervention and drug therapy. However, limited availability of surgical options due to lack of expertise, corneal tissue, and necessary infrastructure, among other reasons, poses challenges. Additionally, drug therapy faces limitations in providing sustained treatment for BK due to low bioavailability of drugs and increasing bacterial resistance. In recent years, novel treatments have emerged as potential breakthroughs in overcoming the deadlock in BK management. These include nanotechnology-based ocular drug delivery systems, nano-antibacterial materials, as well as promising treatment methods such as nanoparticles, nanogels, quantum dots, hydrogels, microneedles, plasma therapy, phage therapy, gene therapy and corneal cross-linking, etc. This article provides a comprehensive review on the research progress made with these innovative approaches aiming to offer new insights into BK treatment strategies. We first analyze the epidemiology and predisposing factors of BK. Then, we summarize the disadvantages of traditional treatment methods. Afterwards, we introduce the research progress of novel therapy and elaborate some details of the research. Finally, we give the conclusion and future perspectives. This review serves as a valuable resource for advancing BK treatment strategies by deepening our understanding regarding the advantages offered by new methodologies. It also provides references for future applications and prospective research in this field.

Keywords:  Bacterial keratitis; Drug delivery; Drug resistance; Nanomaterials; Nanotechnology; Novel treatments

DOI:  https://doi.org/10.1016/j.ijpharm.2025.125793
Antibiotics (Basel). 2025 May 15. pii: 509. [Epub ahead of print]14(5):

Accurate Diagnosis of Pseudomonas aeruginosa Is Critical to Mitigating Development of Antibiotic Resistance.

Hala I Al-Daghistani, Lubna F Abu-Niaaj, Sima Zein.

  Background: The accurate and rapid diagnosis of infections is critical for effective and timely treatment. Misdiagnosis often leads to the prescription of antibiotics not targeting the causing agent of infection and thus be the possible development of multidrug resistance. This collectively worsens the condition and might lead to unnecessary intervention or death. The abundance of Pseudomonas spp. in healthcare-settings and the environment may lead to the inaccurate diagnosis of P. aeruginosa, making the treatment of its infections challenging. P. aeruginosa is a Gram-negative, opportunistic pathogen commonly linked to healthcare-associated infections. Its pathogenicity is attributed to several virulence factors correlated to enhanced survivability and colonization, invasion of the host tissues, and the development of multidrug resistance. When advanced diagnostic facilities are limited or unaffordable, the prescription of antibiotics solely relies on identifying the bacteria by culture-based methods. Objectives: This study aims to validate the accuracy of diagnosis of fifty clinical isolates preidentified as P. aeruginosa in three healthcare facilities in Jordan. Methods: The isolates were from infected areas of patients, including skin, wounds, ears, urine, and peritoneal cavities. Morphological and biochemical tests were performed, and the validation relied on the polymerase chain reaction (PCR) amplification of the 16S ribosomal ribonucleic acid (rRNA) gene. This molecular method is affordable for medical facilities with limited finances in contrast to advanced high-cost techniques. Results: The PCR confirmed that only 60% of the isolates were P. aeruginosa. All the confirmed isolates could produce different pigments and form biofilms. Conclusions: The high percentage of isolates mistakenly identified as P. aeruginosa raises concern about the suitability of prescribed antibiotics. The present study strongly recommends using advanced molecular methods to identify the pathogens. If conventional methods remain the only diagnostic option, this study recommends frequent external validation for tests in addition to performing an antibiotic susceptibility test to pinpoint the effective antibiotics against biofilm-producing P. aeruginosa.

Keywords:  Pseudomonas aeruginosa; antibiotic resistance; pyocyanin; virulence factors

DOI:  https://doi.org/10.3390/antibiotics14050509
Molecules. 2025 May 13. pii: 2144. [Epub ahead of print]30(10):

Biomedical Application of Nanogels: From Cancer to Wound Healing.

Mohammad Zafaryab, Komal Vig.

  Nanogels are polymer-based, crosslinked hydrogel particles on the nanometer scale. Nanogels developed from synthetic and natural polymers have gathered a great deal of attention in industry and scientific society due to having an increased surface area, softness, flexibility, absorption, and drug loading ability, as well as their mimicking the environment of a tissue. Nanogels having biocompatibility, nontoxic and biodegradable properties with exceptional design, fabrication, and coating facilities may be used for a variety of different biomedical applications, such as drug delivery and therapy, tissue engineering, and bioimaging. Nanogels fabricated by chemical crosslinking and physical self-assembly displayed the ability to encapsulate therapeutics, including hydrophobic, hydrophilic, and small molecules, proteins, peptides, RNA and DNA sequences, and even ultrasmall nanoparticles within their three-dimensional polymer networks. One of the many drug delivery methods being investigated as a practical option for targeted delivery of drugs for cancer treatment is nanogels. The delivery of DNA and anticancer drugs like doxorubicin, epirubicin, and paclitaxel has been eased by polymeric nanogels. Stimuli-responsive PEGylated nanogels have been reported as smart nanomedicines for cancer diagnostics and therapy. Another promising biomedical application of nanogels is wound healing. Wounds are injuries to living tissue caused by a cut, blow, or other impact. There are numerous nanogels having different polymer compositions that have been reported to enhance the wound healing process, such as hyaluronan, poly-L-lysine, and berberine. When antimicrobial resistance is present, wound healing becomes a complicated process. Researchers are looking for novel alternative approaches, as foreign microorganisms in wounds are becoming resistant to antibiotics. Silver nanogels have been reported as a popular antimicrobial choice, as silver has been used as an antimicrobial throughout a prolonged period. Lignin-incorporated nanogels and lidocaine nanogels have also been reported as an antioxidant wound-dressing material that can aid in wound healing. In this review, we will summarize recent progress in biomedical applications for various nanogels, with a prime focus on cancer and wound healing.

Keywords:  anticancer; hydrogel; nanogel; wound healing

DOI:  https://doi.org/10.3390/molecules30102144
Infect Dis (Lond). 2025 May 29. 1-27

A group with emerging potential in the clinical and public health realms: the genus Providencia.

J Michael Janda.

   BACKGROUND: The genus Providencia is increasingly being recognized as an important human pathogen. Previously a member of the family Enterobacteriaceae but now reclassified into the family Morganellaceae along with Morganella and Proteus, the phylogenetic depth of this clade has expanded from 3 species in its inception to 12 as of 2025. Recent clinical and epidemiologic data provide convincing evidence that P. alcalifaciens causes gastroenteritis and there is also increasing recognition of carbapenem-resistant strains of P. stuartii and P. rettgeri causing serious infections in hospital settings.
OBJECTIVE AND METHODS: Since 2000, no comprehensive review of this genus has been published detailing taxonomic changes, ecological associations, emerging disease trends, pathogenicity and diagnostic modalities useful in detecting and typing providenciae. The objective of this article is to provide a current review and update of recent publications (PubMed, ScienceDirect, Google Scholar, Scopus®) post-2000 and to summarize results and conclusions to date on this increasingly important genus.
RESULTS: Many reports have now been published describing human cases of enteritis and major outbreaks of gastroenteritis attributed to P. alcalifaciens and supported by multiple epidemiologic lines of evidence including typing methods (serology, molecular), in vivo immune responses, and case-controlled investigations. Similar disease syndromes have also been reported in dogs and pigs with one national canine outbreak of haemorrhagic diarrhoea reported from Norway in 2021. In addition, increasing drug resistance has been noted in both P. stuartii and P. rettgeri leading to the worldwide discovery of multi-, extensive-, and pan-resistant isolates causing disease which presents diagnostic issues in the laboratory and therapeutic challenges.
CONCLUSION: The analysis reveals that providenciae are increasingly being implicated as important causes of intestinal and systemic disease. This is supported by a ten-fold increase in the number of Providencia studies listed in PubMed between 2000 and 2024. Methods need to be developed in the microbiology laboratory to recognize "pathogenic" strains of P. alcalifaciens that produce enteritis from commensal isolates. Emerging antimicrobial resistance needs to be detected early, monitored, and controlled to avoid further dissemination. New infection control prevention procedures need to be advanced and assessed for usefulness in medical care facilities.

Keywords:  Providencia; ecologic associations; gastroenteritis outbreaks; laboratory identification; pathogenicity; taxonomy

DOI:  https://doi.org/10.1080/23744235.2025.2509007
Antibiotics (Basel). 2025 May 14. pii: 504. [Epub ahead of print]14(5):

In Vitro Analysis of Interactions Between Staphylococcus aureus and Pseudomonas aeruginosa During Biofilm Formation.

Julia Scaffo, Rayssa Durães Lima, Cameron Dobrotka, Tainara A N Ribeiro, Renata F A Pereira, Daniela Sachs, Rosana B R Ferreira, Fabio Aguiar-Alves.

  Staphylococcus aureus and Pseudomonas aeruginosa are classified as ESKAPE pathogens that present a significant challenge to treatment due to their increased resistance to a considerable number of antimicrobial agents. Background/Objective: Biofilms exacerbate treatment challenges by providing enhanced antimicrobial and environmental protection. Mixed-species biofilms further complicate treatment options through numerous complex interspecies interactions, leading to potentially severe adverse clinical outcomes.
METHODS: This study assessed the interaction between clinical S. aureus and P. aeruginosa isolates during biofilm formation using microplate biofilm formation assays, scanning electron microscopy, and confocal microscopy.
RESULTS: We identified a competitive relationship between P. aeruginosa and S. aureus, where both pathogens exhibited a reduction in biofilm formation during mixed-species biofilms compared with monocultures, although P. aeruginosa outcompeted S. aureus. Furthermore, we found that the cell-free conditioned media (CFCM) of P. aeruginosa significantly reduced the S. aureus biofilms. Using fractioned CFCM, we identified that the anti-staphylococcal activity of the >10 kDa fraction was almost identical to the non-fractioned CFCM. Our confocal microscopy results suggest that P. aeruginosa CFCM depolarize S. aureus membranes and reduces the biofilm burden.
CONCLUSIONS: These findings contribute to our understanding of the mechanisms underlying the interactions between these pathogens, suggesting that there is an antagonistic relationship between S. aureus and P. aeruginosa in a biofilm setting.

Keywords:  ESKAPE; Pseudomonas aeruginosa; Staphylococcus aureus; antimicrobial resistance; polymicrobial biofilms

DOI:  https://doi.org/10.3390/antibiotics14050504