bims-fagtap 2025-05-25 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–05–25
twenty-two papers selected by
Luca Bolliger, lxBio

Progress in phage therapy in response to antimicrobial resistance.
Limitation of the Lytic Effect of Bacteriophages on Salmonella and Other Enteric Bacterial Pathogens and Approaches to Overcome.
Phage (cocktail)-antibiotic synergism: a new frontier in addressing Klebsiella pneumoniae resistance.
[Application of phages in farm animals, food and the environment as part of a One Health approach-potentials and challenges].
Gut microbiome: Temperate and latent phages are dominant in the human gut.
Phage-antibiotic synergy to combat multidrug resistant strains of Gram-negative ESKAPE pathogens.
Non-antibiotic therapies for multidrug-resistant gastrointestinal infections: an overview of the use of probiotics, natural compounds, and bacteriophages.
Synergistic treatment of linoleic acid and cefazolin on Staphylococcus aureus biofilm-related catheter infections.
Impact of FortiPhi-S bacteriophage solution on the environmental microbiome in poultry litter systems from commercial operations.
Therapeutic and protective approaches to combat Campylobacter jejuni infections.
Ceftobiprole in cystic fibrosis: a case series.
Startups and the next frontier of inflammatory bowel disease therapy: a guide for the brave.
Pharmacomicrobiomics: The role of the gut microbiome in immunomodulation and cancer therapy.
Whole Genome Sequencing-Based Prediction of Antibiotic-Resistance of Ocular Staphylococcus aureus Across Six Continents.
A 10-Year Retrospective Study of Bacterial Infections in a Japanese Regional Hospital: The Impact of COVID-19 and an Earthquake.
Immunometabolism shapes chronic Staphylococcus aureus infection: insights from biofilm infection models.
Microbiological and molecular aspects of periodontitis pathogenesis: an infection-induced inflammatory condition.
Berberine@AgNPs@carboxylated chitosan hydrogel dressing with immunomodulatory and anti-biofilm properties promotes wound repair in drug-resistant bacterial infections.
A polymicrobial perspective into the ecological role of Enterococcus faecalis in dental root canal infections.
Nanocellulose Wound Dressings with Integrated Protease Sensors for Detection of Wound Pathogens.
Impact of Pseudomonas aeruginosa biofilm formation by different sequence types on treating lower limb vascular infections.
Novel antibiotic discovery and the antibiotic resistome.

Virology. 2025 May 15. pii: S0042-6822(25)00191-6. [Epub ahead of print] 110578

Progress in phage therapy in response to antimicrobial resistance.

William Calero-Cáceres, José Luis Balcázar.



Keywords:  Antimicrobial resistance; Bacteriophage genomics; Lytic phages; One health; Phage cocktails; Phage therapy

DOI:  https://doi.org/10.1016/j.virol.2025.110578
Int J Microbiol. 2025 ;2025 5936070

Limitation of the Lytic Effect of Bacteriophages on Salmonella and Other Enteric Bacterial Pathogens and Approaches to Overcome.

Chuan-Wei Tung, Dita Julianingsih, Anna Phan, Christa Canagarajah, Zabdiel Alvarado-Martínez, Debabrata Biswas.

  Bacteriophages (phages) have emerged as promising agents for combating bacterial pathogens, including nontyphoidal Salmonella enterica (S. enterica), the most common foodborne pathogen worldwide. The emergence of antimicrobial-resistant (AMR) S. enterica poses a severe healthcare issue. Nowadays, many countries worldwide have banned antibiotics for animal feeds or additives, and various strategies have been developed and gained popularity for their potential to address S. enterica infection. Among these strategies, phage therapy shows more promise because of its ability to specifically target bacterial pathogens without disrupting the beneficial microbiota or animal/human cells. Phages are viruses that rupture host cells through the lysis of phage-encoded endolysin proteins. Nonetheless, phages also face various challenges, including phage resistance, gene transduction, serovar diversity, and the immune response of animal/human organisms, which limit the efficacy of S. enterica. Due to this limitation of phages, endolysin, as a lytic protein for bacterial cells derived from phages, has been demonstrated as another promising solution against various bacterial pathogens, including AMR. This review is aimed at discussing the benefits and limitations of phage therapies and exploring the promising potential of phage-encoded endolysins in controlling S. enterica.

Keywords:  Salmonella enterica; antibiotic-resistance; bacteriophage; endolysin; food safety; phage therapy

DOI:  https://doi.org/10.1155/ijm/5936070
Front Microbiol. 2025 ;16 1588472

Phage (cocktail)-antibiotic synergism: a new frontier in addressing Klebsiella pneumoniae resistance.

Chandrasekar Karthika, Nambiraman Malligarjunan, Nagaiah Hari Prasath, Shunmugiah Karutha Pandian, Shanmugaraj Gowrishankar.

  Phages, which play a crucial role in regulating bacterial populations and evolution, have gained renewed attention as potential therapeutic agents especially in the face of rising antimicrobial resistance, such as in Klebsiella pneumoniae- a MDR pathogen with significant clinical implications for immunocompromised individuals. In this milieu, the present investigation aimed at evaluating the therapeutic potential of two lytic phages, KPKp (jumbo phage) and KSKp, as potential candidates for phage treatment. Initial purification and TEM characterization revealed their family as Ackermannviridae (KPKp) and Straboviridae (KSKp). The one-step growth curve analysis divulged that KPKp and KSKp exhibit burst sizes of ~98 and ~121 and latency periods of 8 and 12 min, respectively. Genomic analysis unveiled linear double-stranded DNA as their genome with sizes 206,819 bp (KPKp) and 167,101 bp (KSKp) lacking virulence or lysogenic genes, signifying their therapeutic suitability. Evaluation of phages as a cocktail demonstrated a substantial improvement in lytic ability, achieving complete (100%) lysis (at MOI 1) of clinical isolates compared to individual phages, achieving 50 and 25% lysis at MOI 1. In vitro investigations demonstrated that the phage cocktail significantly decreased both planktonic and sessile cells. Additionally, the phage (cocktail)-antibiotic synergism (PAS) achieves over 90% inhibition of K. pneumoniae, even at sub-lethal antibiotic doses. PAS treatment significantly prolongs the lifespan of K. pneumoniae-infected Galleria mellonella. Compared to cocktail phage therapy, PAS demonstrates a superior reduction in bacterial load. In conclusion, the combination of phages and antibiotic holds potential for addressing clinical challenges associated with MDR K. pneumoniae infection.

Keywords:  Galleria mellonella histopathology; Klebsiella pneumoniae; biofilm; cocktail phages antibiotic synergism; jumbo phage; phage therapy; whole genome sequencing

DOI:  https://doi.org/10.3389/fmicb.2025.1588472
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2025 May 20.

[Application of phages in farm animals, food and the environment as part of a One Health approach-potentials and challenges].

Sophie Kittler, Jens A Hammerl.

  In order to ensure the holistic protection of human, animal and environmental health (commonly referred to as One Health), alternatives to the available antimicrobial approaches are required. Although antibiotic drugs have an outstanding broad spectrum of activity, their use is under discussion due to increasingly occurring resistances. Furthermore, the utilisation of antibiotics can result in significant consequences for the affected microbiome, often irreversibly altering its natural composition. The necessity for the implementation of alternative and targeted control measures for bacterial pathogens (e.g. zoonoses) represents a significant challenge for all sectors within the One Health framework. With growing interest, control strategies, some of which have been neglected for centuries, are under discussion for use as valuable tool for safeguarding health across all sectors.Bacteriophages (phages) represent a naturally occurring biological resource with promising potential for use in targeted biocontrol of specific bacteria. As bacterial viruses, they interact specifically with their bacterial hosts, invading them to utilize the bacterial metabolism for their replication, finally destroying the infected bacterial cell. The benefits of this natural predator-prey relationship for the control of bacterial pathogens have long been recognized and extensively studied. This review summarises selected studies on the use of phages, illustrating the potential and application possibilities, but also the challenges of phage use. Due to their cross-sectoral relevance, the use of phages in farm animals, food and the environment is presented as an example.

Keywords:  Antimicrobial resistance; Antimicrobial therapy; Bacteriophages; One Health; Treatment; Zoonoses

DOI:  https://doi.org/10.1007/s00103-025-04055-z
Curr Biol. 2025 May 19. pii: S0960-9822(25)00006-5. [Epub ahead of print]35(10): R377-R379

Gut microbiome: Temperate and latent phages are dominant in the human gut.

Yan Huang, Teng Wang, Yingfei Ma.

Most gut bacteria are lysogens, harboring temperate phages whose induction leads to host lysis and disrupts the microbiome. A recent paper combines mathematical modeling to calculate the virus-to-microbe ratio in the gut and estimates a phage-induction rate of approximately 0.001-0.01 per bacterium per day. This provides new insights into the population dynamics and lifestyle characteristics of human gut phages.

DOI: https://doi.org/10.1016/j.cub.2025.01.006
Sci Rep. 2025 May 18. 15(1): 17235

Phage-antibiotic synergy to combat multidrug resistant strains of Gram-negative ESKAPE pathogens.

Tinta Carmen Morris, Brandon Reyneke, Sehaam Khan, Wesaal Khan.

  Bacteriophage-antibiotic-synergy (PAS) was investigated to target Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Enterobacter cloacae. Whole genome sequencing indicated that bacteriophage KPW17 targeting K. pneumoniae, clustered with genus Webervirus, ECSR5 targeting E. cloacae clustered with Eclunavirus, PAW33 targeting P. aeruginosa clustered with Bruynoghevirus, while ABTW1 targeting A. baumannii clustered with Vieuvirus. PAS analysis showed that the combination of ciprofloxacin (CIP) and levofloxacin (LEV) with PAW33 resulted in the synergistic eradication of all tested P. aeruginosa strains. Similarly, the combined use of doripenem (DOR) and LEV with KPW17 resulted in the synergistic eradication of the environmental and clinical K. pneumoniae strains, while the combined use of DOR and gentamicin (CN) with ECSR5 was synergistic against the clinical E. cloacae NCTC 13406. Gentamicin with ECSR5, however, only exhibited an additive effect for E. cloacae 4L, while ABTW1 with piperacillin-tazobactam (TZP) and imipenem (IPM) resulted in an indifferent interaction between the bacteriophage and tested antibiotics against the clinical A. baumannii AB3, i.e., the activity of the combination is equal to the activity of most active agent. Thus, while the observed PAS may offer an opportunity for the re-introduction or more efficient application of certain antibiotics to combat antibiotic resistance, extensive research is required to determine the optimal phage-antibiotic combinations, dosages and treatment regiments.

Keywords:  Antibiotics; Bacteriophages; Combination therapies; ESKAPE; Pathogens; Synergy

DOI:  https://doi.org/10.1038/s41598-025-01489-y
Front Antibiot. 2025 ;4 1554061

Non-antibiotic therapies for multidrug-resistant gastrointestinal infections: an overview of the use of probiotics, natural compounds, and bacteriophages.

Manuela Oliveira, Áurea Madureira-Carvalho, Ricardo Jorge Dinis-Oliveira, Diana Dias da Silva.

  The worldwide increasing frequency and severity of multidrug-resistant gastrointestinal (MDR-GI) infections not only raises awareness of the debilities of conventional antibiotic treatments but also highlights the demand for alternative interventions. One of these alternatives is probiotics, harmless bacteria that compete with pathogenic species, which have been considered beneficial due to their therapeutic potential since they strengthen the mucosal barrier and modulate the host immune response. Other natural compounds (e.g., polyphenols, flavonoids, and essential oils) present diverse antimicrobial mechanisms, which are promising alternatives to mitigate resistant pathogens. Finally, bacteriophages, viruses that target specific bacteria, constitute a precise approach in which MDR bacteria are lysed or disrupted by the biofilms formed during colonization without compromising the normal gut microbiome. Therefore, the present manuscript provides an integrated perspective on alternative non-antibiotic therapies to manage MDR-GI infections; for this purpose, it covers aspects such as their action mechanisms, current clinical applications, and the challenges that limit their broader application in clinical practice. The potential of combining these approaches or personalizing infection treatments adjusted to patients' microbiome profiles is also discussed, aiming to enhance efficacy and reduce resistance risks. Finally, the importance of continued research and development to optimize these alternatives is also debated, addressing aspects such as the need to surpass regulatory barriers and conducting large-scale clinical trials to establish the safety and efficacy of these non-antibiotic alternatives. This overview of the current knowledge contributes to the ongoing efforts to develop sustainable strategies to combat MDR-GI infections and reduce the global burden of antibiotic resistance.

Keywords:  alternative therapies; antibiotic resistance; biofilm disruption; gut microbiota; immune modulation; microbial interactions; natural compounds

DOI:  https://doi.org/10.3389/frabi.2025.1554061
Appl Environ Microbiol. 2025 May 21. e0077025

Synergistic treatment of linoleic acid and cefazolin on Staphylococcus aureus biofilm-related catheter infections.

Soyoung Ham, Han-Shin Kim, Min Jee Jo, Eunji Cha, Hwa-Soo Ryoo, Hyojin Kim, Heeho Lee, Gang-Jee Ko, Hee-Deung Park.

  Staphylococcus aureus is a human pathogen that causes severe infections through biofilm formation. S. aureus biofilm is particularly susceptible to catheters in patients undergoing peritoneal dialysis. Although antibiotics are used to treat catheter infections, high-concentration treatments adversely affect human host immune systems and change the physicochemical properties of the catheters. To improve therapeutic outcomes without side effects, we combined antibiotics and natural products. In this study, we propose a combination of linoleic acid (LA) and cefazolin (CFZ) to treat S. aureus infections synergistically and apply it to catheter environments and in vivo systems. LA is a polyunsaturated fatty acid derived from natural products, and CFZ is a major antibiotic used to treat S. aureus catheter-related infections. The optimum synergistic condition was determined using silicon pad-forming biofilm similar to catheter materials. S. aureus biofilms were considerably inhibited in vitro and in vivo owing to the improved antibacterial effects. Furthermore, the combination negatively regulated the chemokine levels in the peritoneum, kidney, and liver extracted from mouse models. Moreover, it did not affect the cytotoxicity of human omentum mesothelial cells and the functions of the kidney and liver. Therefore, the combination of LA and CFZ could be a potential synergistic therapy for S. aureus catheter infections.IMPORTANCECatheter contamination is commonly caused by Staphylococcus aureus biofilm formation, primarily in peritoneal dialysis patients. Although antibiotics are used to treat catheter infections, high concentrations of antibiotics impair the immune system of the human host and alter the physicochemical properties of catheters. Therefore, it is crucial to improve therapeutic outcomes while minimizing the side effects of antibiotics. Combined treatments with natural products can be solutions to alleviate these problems. Our study offers a new synergistic combination (linoleic acid and cefazolin) for the control of catheter infections caused by S. aureus biofilms, especially in peritoneal dialysis.

Keywords:  Staphylococcus aureus; catheter biofilm; cefazolin; linoleic acid; synergistic combination

DOI:  https://doi.org/10.1128/aem.00770-25
Poult Sci. 2025 Apr 03. pii: S0032-5791(25)00356-6. [Epub ahead of print]104(8): 105117

Impact of FortiPhi-S bacteriophage solution on the environmental microbiome in poultry litter systems from commercial operations.

Irma Maria Janania Gamez, Mindy M Brashears, Kendra Nightingale, Tyler P Stephens, Carlos E Martinez-Soto, Edith Chow.

  The uprising demand of poultry products has led to an increase in the production of chickens. Nonetheless, this increase also gives way for an uprise in different types of issues such as food safety, human and animal health. While postharvest intervention strategies are considerably studied and established, preharvest food safety is considered more challenging. Therefore, anti-microbials like antibiotics are commonly used in poultry production to address and prevent contamination by pathogens. As a result of the many drawbacks associated with antibiotics, there is a growing demand for alternatives in animal production. Consequently, the use of bacteriophages in this field has been on the rise. This study highlights the effect of the application of the bacteriophage treatment FortiPhi-S on commercial poultry litter at different concentrations. The results demonstrate a significant difference by decreasing the richness of samples and increasing the diversity. The treatment also reduced the pathogenic families Staphylococcaceae and maintaining beneficial families such as Lachnospiraceae and Bacteroidaceae. Furthermore, pathogenic strains of Salmonella, Clostridia, and Escherichia-Shigella were significantly reduced or eliminated. The results demonstrated that the bacteriophage treatment FortiPhi-S has a significant effect on the microbial composition and diversity of poultry litter.

Keywords:  Bacteriophage; Litter; Microbiome; Poultry; Salmonella

DOI:  https://doi.org/10.1016/j.psj.2025.105117
Front Pharmacol. 2025 ;16 1572616

Therapeutic and protective approaches to combat Campylobacter jejuni infections.

Irshad Sharafutdinov, Bodo Linz, Nicole Tegtmeyer, Steffen Backert.

  Campylobacter jejuni is a typical zoonotic bacterium, colonizing the gut of many bird species as commensal. In humans, C. jejuni is a major foodborne pathogen. Infection of humans causes campylobacteriosis in the small intestine, constituting a main source of bacteria-dependent gastroenteritis cases worldwide. In particular, the ingestion of under-cooked rooster meat, raw milk and contaminated water, as well as cross-contamination of ready-to-eat food after handling raw chicken meat, are responsible for the majority of C. jejuni infections. As a consequence, infected individuals may acquire watery and/or bloody diarrhea associated with abdominal pain, and eventually post-infection illnesses of the neural system and joints, including the Guillain-Barré, Miller Fisher and Reiter syndromes. One therapeutic strategy is to reduce C. jejuni colonization in chicken farms using vaccination, bacteriocins and phage therapy protocols. Prevention approaches during poultry meat processing comprise the compliance to high hygiene standards. Furthermore, substantial progress has been also made in recent years to combat campylobacteriosis using established mouse and in vitro cell model systems. In this regard, specific C. jejuni colonization- and pathogenicity-associated components were considered as favored treatment structures, targeting bacterial movement, host cell interaction, intracellular survival, propagation and spread of the bacteria. This has been complemented by a number of pharmaceutical compounds to reduce C. jejuni-induced epithelial cell damage, inflammation and apoptosis in infected mice. Here we review these novel treatment and prevention as well as "One World - One Health" approaches that aim to diminish the consequences of acute campylobacteriosis and post-infection sequelae in humans.

Keywords:  Campylobacterjejuni; One Health; bacteriophage; epithelial barrier; gut microbiota; phytochemicals; probiotics; vaccine

DOI:  https://doi.org/10.3389/fphar.2025.1572616
JAC Antimicrob Resist. 2025 Jun;7(3): dlaf077

Ceftobiprole in cystic fibrosis: a case series.

Lisa Nwankwo, Silke Schelenz, Newara Ramadan.

Background: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance (CFTR) gene, resulting in the secretion of hyperviscous mucus. Infective exacerbations are a major determinant of morbidity and mortality in CF patients. These infections are clinically challenging, and antimicrobial treatment should effectively target the organisms and be delivered early to improve survival. Ceftobiprole is a fifth-generation cephalosporin antibiotic that is not indicated for the treatment of CF. However, due to its activity against common causes of infective exacerbations in CF such as Staphylococcus aureus, including MRSA, and Pseudomonas aeruginosa where resistance has not developed, it has utility for managing infective exacerbations.
Objectives: To describe the use of ceftobiprole in the treatment of infective exacerbations in CF.
Patients and methods: Ten patients with CF (age 24-63; six male and four female) were treated with ceftobiprole for infective exacerbations following discussion within the multi-disciplinary team. In most patients, ceftobiprole was given concomitantly with other antibiotics.
Results: All patients had positive sputum cultures for S. aureus (including nine MRSA), and seven patients had concomitant P. aeruginosa infection. Ceftobiprole treatment was associated with improved lung function, and markers of systemic inflammation decreased for most patients, with some variation. There was good tolerability in all but four patients.
Conclusions: Ceftobiprole presents a therapeutic option for susceptible infections in CF patients with limited treatment options. Its broad-spectrum coverage may help to reduce polypharmacy. However, further clinical studies are needed.

DOI: https://doi.org/10.1093/jacamr/dlaf077
Curr Opin Gastroenterol. 2025 May 02.

Startups and the next frontier of inflammatory bowel disease therapy: a guide for the brave.

Vladimir Lamm.

   PURPOSE OF REVIEW: This review explores the evolving landscape of inflammatory bowel disease (IBD) therapy, particularly through the lens of startups that are pushing the boundaries of current treatment paradigms. By discussing the challenges and opportunities faced by startups, this review seeks to provide insights for aspiring entrepreneurs and innovators in the IBD space.
RECENT FINDINGS: The landscape of IBD is rapidly evolving, with innovative solutions ranging from novel therapeutics to digital health platforms. An analysis of recent SBIR award winners highlights emerging trends, including microbiome-based therapies, targeted small molecules, and advanced drug delivery systems like hydrogels. Digital health solutions, such as smart monitoring tools and AI-assisted treatment selection are gaining traction. IBD startups are playing a crucial role in cost reduction through competition, streamlining drug development, and treatment personalization. Despite regulatory, financial, and funding challenges, startups are driving the next phase of IBD innovation.
SUMMARY: The future of IBD therapy is being driven by innovative start-ups that are challenging the status quo in IBD treatment. These companies are addressing critical gaps in therapy by focusing on novel drug targets, improved drug delivery, and precision medicine. While startups face many challenges including high research and development (R&D) costs, regulatory hurdles, and funding, they continue to be at the forefront of IBD innovation. Their success could potentially lead to more affordable and effective therapies. By drawing on examples like the nutraceutical company, Evinature, my own personal experience as technical lead of Edulis, a startup focused on localized IBD therapy, and perspective from the head of the Crohn's and Colitis Foundation's IBD Ventures, this review aims to provide insights for those looking to innovate in IBD.

Keywords:  entrepreneurship; healthcare cost; innovation

DOI:  https://doi.org/10.1097/MOG.0000000000001100
Gastroenterology. 2025 May 15. pii: S0016-5085(25)00755-3. [Epub ahead of print]

Pharmacomicrobiomics: The role of the gut microbiome in immunomodulation and cancer therapy.

Laura A Bolte, Johannes R Björk, Ranko Gacesa, Rinse K Weersma.

  There is a large heterogeneity among individuals in their therapeutic responses to the same drug and in the occurrence of adverse events. A key factor increasingly recognized to contribute to this variability is the gut microbiome. The gut microbiome can be regarded as a second genome, holding significant metabolic capacity. Consequently, the field of pharmacomicrobiomics has emerged as a natural extension of pharmacogenomics for studying variations in drug responses. Pharmacomicrobiomics explores the interaction of microbiome variation with drug response and disposition. The interaction between microbes and drugs is, however, complex and bidirectional. While drugs can directly alter microbial growth or influence gut microbiome composition and functionality, the gut microbiome also modulates drug responses directly through enzymatic activities and indirectly via host-mediated immune and metabolic mechanisms. Here we review recent studies that demonstrate the interaction between drugs and the gut microbiome, focusing on cancer immunotherapy and immunomodulation in the context of inflammatory bowel disease and solid organ transplantation. Since the gut microbiome is modifiable, pharmacomicrobiomics presents promising opportunities for optimizing therapeutic outcomes, with recent clinical trials highlighting fecal microbiota transplantation as a strategy to enhance the efficacy of immune checkpoint blockade. We also shed light on the future perspectives for patients arising from this field. While multiple lines of evidence already demonstrate that the gut microbiome interacts with drugs, and vice versa, thereby affecting treatment efficacy and safety, well-designed clinical studies and integrated in vivo and ex vivo models are necessary to obtain consistent results, improve clinical translation and further unlock the gut microbiome's potential to improve drug responses.

Keywords:  Drug response; Immune Checkpoint Inhibitors; Inflammatory Bowel Diseases; Microbiome; Organ Transplantation

DOI:  https://doi.org/10.1053/j.gastro.2025.04.025
Exp Eye Res. 2025 May 21. pii: S0014-4835(25)00196-4. [Epub ahead of print] 110425

Whole Genome Sequencing-Based Prediction of Antibiotic-Resistance of Ocular Staphylococcus aureus Across Six Continents.

Jiawei Shen, Muhammad Yasir, Mark Willcox.

  Staphylococcus aureus is a leading cause of ocular infections, resulting in vision loss in severe cases. Understanding the antibiotic resistance profiles of ocular S. aureus can help customize treatments. However, there is a lack of global data on the resistance patterns of ocular isolates and comparative regional analyses. Hence, WGS data from 195 ocular S. aureus isolates across six continents were analysed to identify antibiotic resistance genes (ARGs) and predict antibiotic resistance phenotypes in this study. A total of 40 ARGs were detected, involving resistance mechanisms against aminoglycosides, beta-lactams, macrolide-lacosamide-streptogramin B (MLSB), glycopeptides, tetracyclines, other antibiotic classes, and efflux pump regulators. Notably, the prevalences of ARGs associated with efflux pump regulators and beta-lactams were particularly high (>80%). Resistance to 45 antibiotics was predicted across the isolates, with 51% identified as multidrug-resistant (MDR), while only 8% were predicted to be fully susceptible to all predicted antibiotics. Regional data varied, with isolates from North America and Asia exhibiting the most extensive resistance patterns, showing predicted resistance to 45 and 41 antibiotics, respectively. In contrast, Oceanian isolates were predicted to be resistant to only 14 antibiotics. Beta-lactams showed the highest predicted resistance prevalence among all antibiotic classes. Notably, North American isolates showed markedly higher resistance to MLSB antibiotics. A high proportion of cloud genes highlights the need for monitoring regional resistance. This study provides antibiotic resistance profiles among ocular S. aureus using WGS prediction, emphasizing the importance of regional surveillance and antimicrobial stewardship to suggest effective treatment strategies. It is recommended that WGS of more strains be deposited to overcome limited data, and laboratory tests be performed to analyse the consistency between genetic predicted and phenotypic resistance.

Keywords:  AMR; Geographical distribution; WGS; eye infection; resistance genes

DOI:  https://doi.org/10.1016/j.exer.2025.110425
Cureus. 2025 Apr;17(4): e82737

A 10-Year Retrospective Study of Bacterial Infections in a Japanese Regional Hospital: The Impact of COVID-19 and an Earthquake.

Takuya Sakamoto, Tomoyuki Ushimoto, Junji Moriya, Haruki Takikawa, Shinji Akitomi, Tsugiyasu Kanda, Yuji Kasamaki.

  Bacterial infections are a leading cause of patient mortality, and antimicrobial resistance continues to pose a growing global health and economic threat. The combined effects of the COVID-19 pandemic and earthquakes may have influenced patterns of bacterial infections. This study analyzed data on antimicrobial-resistant and susceptible bacteria over a 10-year period (2015-2024), encompassing these natural disasters. During the COVID-19 pandemic, the number of positive bacterial cultures declined and continued to decrease following the earthquake. This trend included antimicrobial-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis (MRSE). Notably, MRSE cases significantly declined during the pandemic period. In addition, infections caused by drug-sensitive Streptococcus pneumoniae among inpatients and Pseudomonas aeruginosa among outpatients showed a significant reduction, with both continuing to decline in the post-pandemic period. In contrast, Legionella infections significantly increased in both the number and frequency of positive cases, a trend that persisted after the 2024 earthquake. These findings differ from previously reported global data. In Japan, widespread mask usage continued even after the pandemic subsided. The results underscore the importance of improving infection control equipment and promoting individual awareness of infection prevention to reduce the risk of future bacterial infections.

Keywords:  antimicrobial bacteria; covid-19; earthquake; inpatients; legionella; outpatients

DOI:  https://doi.org/10.7759/cureus.82737
Curr Opin Microbiol. 2025 May 22. pii: S1369-5274(25)00034-7. [Epub ahead of print]86 102612

Immunometabolism shapes chronic Staphylococcus aureus infection: insights from biofilm infection models.

Adedayo E Ogunware, Tammy Kielian.

Staphylococcus aureus is both a commensal bacterium and versatile pathogen, capable of transitioning from a benign colonizer to cause invasive disease. Its ability to form biofilm - a resilient, highly structured bacterial community - plays a key role in chronic infections, including those associated with medical implants and native tissues. The unique microenvironments of these biofilm niches create challenges for the host immune system, complicating pathogen clearance. Immunometabolism, the interplay between immune function and metabolic programming, plays a crucial role in dictating how the host combats S. aureus biofilms. Leukocytes undergo profound metabolic changes in response to biofilm, which can lead to dysregulated immune responses and persistent infection. This review explores recent insights defining the metabolic landscape of immune responses to S. aureus biofilm with a focus on two clinically relevant models, namely, craniotomy and prosthetic joint infection.

DOI: https://doi.org/10.1016/j.mib.2025.102612
Front Cell Infect Microbiol. 2025 ;15 1533658

Microbiological and molecular aspects of periodontitis pathogenesis: an infection-induced inflammatory condition.

Mina Yekani, Masoumeh Dastgir, Samaneh Fattahi, Shahriar Shahi, Solmaz Maleki Dizaj, Mohammad Yousef Memar.

  Periodontitis (PD) is the most common oral infectious disease. The primary etiologic cause of the onset and development of PD is dental plaque, which consists of bacterial biofilm domiciled within a complex extracellular mass. In PD patients, there is a progressive breakdown of the periodontal ligament and the alveolar bone. In more advanced stages, tooth loss occurs. The progression of this chronic inflammatory disease involves interactions among numerous microbial pathogens particularly, bacteria, the host's immune factors, and various environmental factors. Due to persistent infection by periodonto-pathogenic bacteria, there is an impairment of both innate and acquired immunity, leading to tissue destruction. Chronic inflammation in PD may be associated with several systemic diseases, including cardiovascular conditions, respiratory issues, diabetes, neurological diseases, cancer, and adverse pregnancy outcomes. Antibiotic treatment is one of the effective strategies for treating PD cases, although the emergence of some resistant strains may limit the effectiveness some antibiotics. In this review study, we discussed the main bacteria in PD, the interaction with the immune response, the pathogenesis of bacteria in PD and antibiotic treatment. We also outlined the emergence of resistance to antibiotics among these pathogens.

Keywords:  biofilm; inflammation; microbiology; periodontitis; treatment

DOI:  https://doi.org/10.3389/fcimb.2025.1533658
Int J Biol Macromol. 2025 May 21. pii: S0141-8130(25)05048-2. [Epub ahead of print] 144496

Berberine@AgNPs@carboxylated chitosan hydrogel dressing with immunomodulatory and anti-biofilm properties promotes wound repair in drug-resistant bacterial infections.

Xiaoqi Wang, Jue Hu, Chunjing Chen, Jun Lu, Chang Liu, Yi Ning, Fangguo Lu.

  Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial strain resistant to multiple antibiotics frequently encountered in clinical settings. Excessive antibiotic use has increased bacterial resistance, leaving a lack of effective treatments for MRSA infections. MRSA often colonizes the surface of skin wounds, resulting in chronic inflammation and protracted wound healing. The biofilm formation hinders the complete eradication of the bacteria, exacerbating the local inflammatory response and impeding wound healing. This study presents an innovative methodology for managing MRSA-infected skin wounds. The novel immunomodulatory hydrogel composed of Berberine, silver nanoparticles (AgNPs), and carboxylated chitosan (designated as Ber@AgNPs@CHI hydrogel) demonstrates enhanced therapeutic efficacy in a murine model of MRSA skin infection. This hydrogel is effective in eradicating MRSA and preventing biofilm formation. Furthermore, it modulates the local immune microenvironment by facilitating the transition of macrophages from the M1 to M2 phenotype and increasing the production of vascular endothelial growth factor (VEGF). These actions collectively facilitate the progression of the wound from the inflammatory to the proliferative phase, enhancing the early stages of wound healing. Hence, this safe and effective hydrogel mediates wound healing from multiple perspectives and targets, providing a new potential avenue for treating persistent infected wounds caused by clinical MRSA.

Keywords:  Anti-biofilm; Hydrogel drug delivery system; Immune regulation; Multidrug-resistant bacteria; Wound healing

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.144496
NPJ Biofilms Microbiomes. 2025 May 22. 11(1): 83

A polymicrobial perspective into the ecological role of Enterococcus faecalis in dental root canal infections.

Ana Parga, Jade Mattu, Georgios N Belibasakis, Kimberly A Kline, Julian G Leprince, Daniel Manoil.

Enterococcus faecalis, a non-oral nosocomial pathogen, intriguingly ranks among the most frequently retrieved species from polymicrobial infections of dental root canals. This review integrates findings from the latest omics approaches, alongside emerging evidence of E. faecalis interactions within oral polymicrobial communities, to refine our understanding of its role in these infections. Herein, E. faecalis emerges as an ecologically invasive species and a catalyst of the pathogenicity of entire communities.

DOI: https://doi.org/10.1038/s41522-025-00722-w
ACS Sens. 2025 May 20.

Nanocellulose Wound Dressings with Integrated Protease Sensors for Detection of Wound Pathogens.

Olof Eskilson, Emanuel Wiman, Nina Reustle, Jakob Langwagen, Zeljana Sotra, Anna Svärd, Robert Selegård, Yağmur Baş, Linn Berglund, Kristiina Oksman, Torbjörn Bengtsson, Johan P E Junker, Hazem Khalaf, Daniel Aili.

  Wound infections result in delayed healing, morbidity, and increased risks of sepsis. Early detection of wound infections can facilitate treatment and reduce the need for the excessive use of antibiotics. Proteases are normally active during the healing process but are overexpressed during infection as part of the inflammatory response. Proteases are also produced by the bacteria infecting the wounds, making proteases a highly relevant biomarker for infection monitoring. Here, we show a fluorescence turn-on sensor for real-time monitoring of protease activity in advanced nanocellulose wound dressings for rapid detection of wound pathogens. Colloidal gold nanoparticles (AuNPs) were adsorbed on bacterial cellulose (BC) nanofibrils by using a carefully optimized self-assembly process. The AuNPs could either be homogeneously incorporated in BC dressings or 3D printed in wood-derived cellulose nanofiber (CNF) dressings using a BC-AuNP ink. The BC-adsorbed AuNPs were subsequently functionalized with fluorophore-labeled protease substrates. Cleavage of the substrates by proteases produced by the wound pathogens Staphylococcus aureus and Pseudomonas aeruginosa resulted in a significant increase in fluorescence that correlated with the growth phase of the bacteria. Wound dressing with integrated sensors for the detection of proteolytic activity can enable the sensitive and rapid detection of infections, allowing for optimization of treatment and reducing the risks of complications.

Keywords:  bacteria; gold nanoparticles; nanocellulose; protease; wound infection

DOI:  https://doi.org/10.1021/acssensors.4c03428
Curr Res Microb Sci. 2025 ;8 100379

Impact of Pseudomonas aeruginosa biofilm formation by different sequence types on treating lower limb vascular infections.

Yudi Wang, Qian Xiao, Qiong Yang, Yulin Long, Zhibiao Jiang, Tantao Zhang, Ying Hu, Bingru Gao, Xuanyu Chen, Ting Wang, Linlin Xiao.

  Pseudomonas aeruginosa is a major contributor to persistent chronic infections in clinical practice, owing to its robust biofilm formation capacity and frequent antimicrobial resistance acquisition. However, most current studies focus on single strains and thus overlook phenotypic differences among coexisting strains within the same host. With that in mind, we proposed a hypothesis that P. aeruginosa strains from the same patient, yet with distinct genetic backgrounds, might exhibit differing resistance profiles and virulence genes. To test this hypothesis, we selected three strains with different sequence types (STs), all isolated from the chronic wounds of a patient with long-term bilateral lower limb infections. By employing multilocus sequence typing, antimicrobial susceptibility testing, biofilm gene quantification, growth kinetics assays, Galleria mellonella virulence experiments, and phylogenetic reconstruction, we systematically evaluated the relationships between these strains'biofilm formation and virulence. The results revealed significant genetic diversity and evolutionary origin variations among the three strains. Notably, ST2584 (WYDPA-23-3) exhibited multidrug resistance (resistant to 7 of the 12 tested antibiotics) and the highest growth rate, whereas ST270 (WYDPA-23-2)-despite the downregulation of pelA, a gene linked to extracellular matrix biogenesis-demonstrated a 2.3-fold increase in biofilm formation and the highest larval lethality. By comparing multiple strains coexisting in the same host, this study further elucidates the role of P. aeruginosa biofilm in sustaining chronic infections and offers valuable guidance for optimizing clinical treatment strategies and antibiotic selection. In light of these findings, developing rapid and precise biofilm detection methods and designing innovative drugs targeting high biofilm-producing strains should be prioritized.

Keywords:  Antimicrobial resistance genes; Biofilm; Multidrug resistance; Pseudomonas aeruginosa; Virulence genes

DOI:  https://doi.org/10.1016/j.crmicr.2025.100379
Expert Opin Drug Discov. 2025 May 21. 1-15

Novel antibiotic discovery and the antibiotic resistome.

Rustam Aminov.

   INTRODUCTION: The success of antibiotics in the therapy of infectious diseases is overshadowed by almost inevitable emergence and dissemination of resistances toward these agents, which results in higher morbidity and mortality rates and increased costs. New strategies are now needed to both limit the risk of resistance and to discover new drugs that are efficacious.
AREAS COVERED: This review investigates the resistance problems through evolutionary lenses to better understand and potentially design improved therapeutics for infectious diseases. Furthermore, it gives an overview of the evolutionary history of antibiotic resistance genes and antibiotic biosynthesis genes/clusters, the structures of natural resistomes, and the regulatory roles of antibiotics. The author utilized ScienceDirect, PubMed, Web of Science and Google Scholar using the article's keywords and their combinations to retrieve the most relevant and up-to-date information.
EXPERT OPINION: Antibiotics and their corresponding resistances are ancient phenomena with their evolutionary timescales measured over a vast amount of time. Humans have also benefitted from access to, and the use of, a diverse range of antibiotics for many years also but have disrupted the balance by producing and using enormous amounts of antibiotics that have not existed before in natural ecosystems. This selective pressure has resulted in a tremendous expansion of resistomes. Future antibiotic discovery and development may need to pivot from exploiting extant antibiotic scaffolds and bacterial targets to reduce the risk of the rapid emergence of resistance from existing resistomes.

Keywords:  Antibiotics; antibiotic biosynthesis; antibiotic resistance; cryosols; environment; evolution; permafrost; phylogeny

DOI:  https://doi.org/10.1080/17460441.2025.2490838