Search Results (266)

Salmonella remains one of the most critical zoonotic pathogens in the poultry sector, linked to animal disease, foodborne illness, and the global crisis of antimicrobial resistance (AMR). Poultry acts as a major reservoir, enabling Salmonella transmission from hatchery to retail products through horizontal, vertical, and environmental routes. Despite the use of biosecurity, vaccination, antibiotics, and chemical decontamination, effective and sustainable control across the poultry value chain remains difficult, particularly in the face of rising multidrug-resistant strains and growing consumer concerns over chemical residues. Bacteriophages (phages), viruses that selectively infect and lyse bacteria, have emerged as a promising biological alternative for Salmonella control. Although many studies have reported the effectiveness of phages against bacterial species, including Salmonella, in the poultry industry, reports on their full potential to combat antimicrobial-resistant Salmonella across the entire poultry value chain remain limited. Therefore, this review synthesizes current evidence on the application of phages throughout the poultry value chain, including on-farm interventions, processing plant decontamination, and food packaging and storage. Findings from the reviewed articles indicate over a 90% reduction in Salmonella spp. in poultry farms and post-harvest meat, along with lower mortality in phage-treated groups compared to untreated groups; however, these outcomes depend on several factors (e.g., phage strains, concentrations, application methods, and environmental conditions). Laboratory, pilot, and field studies consistently demonstrate that phage preparations, especially when formulated as cocktails or combined with complementary interventions, can achieve substantial reductions in Salmonella, including antibiotic-resistant serovars, in live birds, eggs, poultry environments, and meat products. Unlike antibiotics and chemical sanitizers, phages act with high specificity, preserving beneficial microbiota and maintaining the sensory and nutritional quality of poultry products. Their safety has been supported by toxicological and genomic assessments, and several phage-based products have obtained regulatory approval, including Generally Recognized as Safe (GRAS) status for food applications in the United States. By integrating efficacy, safety, regulatory, and practical deployment data, this review highlights bacteriophages as a scientifically validated and One Health–aligned tool capable of reducing Salmonella transmission from farm to fork across the poultry value chain, thereby laying the foundation for their future adoption in the poultry industry. Phage-based interventions offer a sustainable pathway to enhance food safety, limit antimicrobial resistance (AMR) dissemination, and strengthen consumer confidence in poultry products. However, the major limitation is the emergence of phage-resistant bacterial strains, as well as the potential involvement of some phages in the transfer of resistance and virulence genes, which could raise public concern. Nevertheless, the use of phage cocktails and whole-genome sequencing, involving tools such as ResFinder and virulence finder, can facilitate the selection of safe phages for application. Full article

Background/Objectives: Burn injuries represent a global public health concern, accounting for approximately 265,000 deaths annually and often leading to severe infections. With the increasing prevalence of multidrug-resistant (MDR) bacteria, innovative therapeutic strategies such as nanoparticle-based topical formulations have gained attention. This study proposed the development of a hydrogel for burn treatment containing biogenic silver nanoparticles (BioAgNPs), hyaluronic acid (HA), and allantoin (AL). Methods: BioAgNPs were previously characterized by transmission electron microscopy (TEM) and incorporated into a hydrogel containing HA and AL, which was physicochemically characterized by pH, spreadability, and energy-dispersive X-ray spectroscopy (EDX). Antibacterial activity was evaluated by broth microdilution, agar diffusion, and time–kill assays against standard and MDR bacterial strains. Cytotoxicity was assessed using the MTT assay in L929 cells, and wound-healing potential was investigated through an in vitro scratch assay to evaluate cell migration and proliferation. Results: BioAgNPs exhibited antibacterial activity against reference strains and MDR isolates, determining the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). HA and AL were non-toxic, while BioAgNPs demonstrated low cytotoxic activity. Although HA and AL did not exhibit antibacterial properties, they promoted cell migration and proliferation. The formulation exhibited physicochemical and pharmaceutical stability, showing suitable properties for topical use, and presented significant antimicrobial action, with bacterial elimination occurring within 2 h of contact, except for S. aureus. Conclusions: Thus, the hydrogel presents a promising alternative for the topical treatment of infected burns, with potential application in combating multidrug-resistant bacteria, being able to eliminate MDR Acinetobacter baumannii. Full article

Background/Objectives: Biofilms are a form of defense that enables bacteria to withstand antibiotic pressure and demonstrate antibiotic resistance. It is crucial to develop anti-biofilm strategies in order to combat chronic and persistent multidrug-resistant (MDR) infections. Methods: In this study, we developed 3D biofilms of single-, dual-, and poly-species MDR ESKAPE components, including the pathogens P. aeruginosa S. aureus and K. pneumoniae, in CF Mu3Gel. We evaluated the efficacy of using a phage, a di-hetero phage cocktail or a poly-hetero phage cocktail in combination with ciprofloxacin to eliminate mature biofilm biomass after 72 h or one week in a single treatment. Results: The phage components mostly exhibited synergistic behavior when combined with ciprofloxacin and with each other in di- and poly-hetero-cocktails. The reduction in 72-h dual- and poly-species biofilms was one log higher than that of one-week biofilms treated with the phage–antibiotic combination. The greatest reductions were observed in the 72-h single-species biofilm with combination therapy, at 1.4–3.0 log. Reductions of 2.16 and 1.6 log were observed in the dual-species P. aeruginosa and S. aureus biofilm and the poly-species biofilm, respectively. Conclusions: This study examined how a single application of phages or phage cocktails, either alone or in combination with ciprofloxacin, impacted established biofilm models, and how this affected the proportion of microcolonies of different species within each model. These insights will facilitate the development of strategies for multiple follow-up treatments, as well as the reordering of phages, phage cocktails, and combinations with antibiotics, to improve outcomes. The 3D biofilm models developed here could be used to screen phages or phage cocktails either on their own or alongside other therapies. This would facilitate the application of in vitro findings to real physiological settings. Full article

ESKAPE pathogens represent a critical threat to global health. This challenge necessitates the development of novel antibacterial strategies. We investigated the antimicrobial potential of NK-92 cells and their derived large extracellular vesicles using flow cytometry, ELISA, confocal microscopy and microbiology assays. Here, we show that both NK-92 cells and NK-92-derived LEVs can interact with bacteria, as confirmed by confocal microscopy and flow cytometry. This interaction is associated with inhibition of colony formation. A possible mechanism can involve defensin-α1 secreted by NK-92 and packed in their LEVs. NK-92-derived LEVs can modulate S. aureus viability, colony growth and clindamycin susceptibility. These findings suggest NK cell-derived LEVs as promising strategies to combat multidrug-resistant bacterial infections. Full article

Background/Objectives: Multidrug-resistant (MDR) Gram-negative bacteria represent a significant public health concern worldwide, particularly in resource-limited settings. In Ghana’s Tamale Metropolis, limited data exist on the prevalence and trends of MDR bacteria, posing challenges to effective antimicrobial stewardship. Methods: This study analyzed microbiological data from 2020 to 2023 to address these knowledge gaps. Results: Among the 4859 clinical samples analyzed, 1570 (33.7%) yielded Gram-negative bacterial isolates, with an MDR prevalence of 40.6%. The most frequently isolated organisms were Klebsiella spp. (28.9%) and Escherichia coli (20.4%). Resistance to cephalosporins (51%) and ciprofloxacin (46%) was particularly pronounced, highlighting the diminishing efficacy of commonly used antibiotics. Older adults (aged 60 years and above) presented the highest MDR prevalence, reflecting the vulnerability of this demographic group. Conclusion:These findings underscore the urgent need for enhanced antimicrobial stewardship programs, improved infection prevention and control measures, and continuous resistance monitoring to combat the growing threat of MDR bacteria in the region. Strengthening laboratory capacity and adherence to strict antibiotic usage policies are crucial for reducing the burden of MDR infections and improving patient outcomes. Full article

In recent decades, antibiotic-resistant bacteria have become an increasingly urgent public health concern. The uncontrolled use of antibiotics, along with inadequate implementation of prevention and control measures, is the primary factor contributing to this issue. The hospital environment is a major source of multidrug-resistant bacteria, and in recent years, there has been growing concern about hospital wastewater, which acts as a significant reservoir for these bacteria and their resistance genes. This situation leads to the spread of multidrug-resistant bacteria in the environment. One particular concern is Acinetobacter, especially Acinetobacter baumannii, which has emerged as a pathogenic threat in healthcare-associated infections. This bacterium is found in high densities in hospital wastewater. Most strains of A. baumannii express resistance not only to carbapenems but also to several other classes of antibiotics, including tetracyclines, fluoroquinolones, and aminoglycosides. These strains must be combated through effective measures. Bacteriophages represent a potential mitigation strategy for antibiotic-resistant Acinetobacter spp. originating from hospital wastewater. This review summarizes studies from online databases regarding the identification and characterization of Acinetobacter strains in hospital wastewater worldwide, and presents progress in isolating and characterizing bacteriophages against A. baumannii found in hospital wastewater. Full article

Background: The global rise in multidrug-resistant (MDR) Gram-negative bacteria (GNB) poses an urgent challenge for infection control and antibiotic stewardship. Among these, Klebsiella pneumoniae is a major cause of hospital-acquired infections and is listed as a critical priority pathogen by the World Health Organization. Peru reports an exceptionally high prevalence of MDR K. pneumoniae, underscoring the need for innovative antimicrobial approaches. Methods: Here, we describe the isolation and characterization of lytic Klebsiella bacteriophage from sewage samples collected from the Huatanay River (Cusco, Peru) in 2023. Phages were isolated using the reference strain MDR K. pneumoniae ATCC BAA-2814. Then, they were screened against 50 clinical MDR K. pneumoniae strains. Results: The phage H33IIK demonstrated effective antibacterial capability, showing strict host specificity for K. pneumoniae, thermal stability, moderate pH tolerance, and high burst size. Whole-genome sequencing analysis classified it within the class Caudoviricetes, family Ackermannviridae, and genus Taipeivirus. The genomic analysis confirmed the absence of lysogeny-related, antimicrobial resistance, and virulence genes, supporting its suitability and safety for potential biotechnological applications. Conclusions: These findings highlight phage H33IIK as a lytic agent effective against MDR K. pneumoniae. It could contribute to the development of phage-based approaches to combat MDR GNB. Full article

Background: Infections caused by multidrug-resistant bacteria and inadequate vaccine coverage against opportunistic pathogens highlight the need for interventions that broadly and durably enhance host defense beyond antigen-specific adaptive immunity. Trained immunity, driven by metabolic and epigenetic reprogramming of innate immune cells, has been predominantly characterized using Bacille Calmette–Guérin and β-glucan, whereas its induction by Gram-negative bacteria remains poorly defined. To address this gap, we aimed to determine whether heat-killed Klebsiella pneumoniae (HK Kp) induces trained immunity through metabolic and hematopoietic reprogramming to confer heterologous antibacterial protection. Methods: HK Kp-trained murine bone marrow-derived macrophages and HK Kp-immunized C57BL/6 mice were employed to interrogate functional, metabolic, and transcriptomic reprogramming in vitro, hematopoietic progenitor remodeling in vivo, and protective efficacy against systemic Salmonella Typhimurium and Staphylococcus aureus infection. Results: HK Kp-trained macrophages showed markedly enhanced IL-1β secretion across all restimulation conditions, stimulus-dependent amplification of TNF-α responses, increased phagocytosis, and improved intracellular control of S. typhimurium, together with sustained upregulation of the glycolytic enzymes-encoding genes Hk2 and Pfkfb3. Transcriptomic profiling revealed extensive reprogramming enriched in glycolysis/gluconeogenesis and hematopoietic cell lineage pathways. In vivo, HK Kp immunization shifted bone marrow stem/progenitor compartments toward a myeloid-biased state. HK Kp-trained mice challenged with lethal S. typhimurium or S. aureus exhibited less weight loss, improved survival rates, and reduced bacterial burdens. Conclusions: Inactivated K. pneumoniae orchestrates metabolic and hematopoietic reprogramming to establish enhanced innate immune responsiveness and confer heterologous protection in murine S. typhimurium and S. aureus sepsis models, supporting its potential as a potent inducer of trained immunity. These findings establish HK Kp-based trained immunity as a promising strategy for combating multidrug-resistant and vaccine-evading pathogens. Full article

Antimicrobial resistance (AMR) threatens global health, particularly through the rise of multidrug-resistant tuberculosis (MDR-TB) and other critical bacterial infections such as methicillin-resistant Staphylococcus aureus (MRSA). Rifamycins remain frontline antibiotics but are increasingly undermined by resistance. Here, we introduce a click-enabled platform for the synthesis of C8-functionalized rifamycins, which can be converted in a single additional step into efficacious 3′-hydroxy-5′-aminobenzoxazinorifamycins (bxRifs) and enzymatically into 25-deacetylated rifamycins (deAcRifs), providing access to novel antibacterial scaffolds that expand beyond the scope of traditional C8 modifications. Accordingly, we establish a modular strategy for late-stage analog development of the complex natural product rifamycin S, wherein azido and alkyne functionalities are installed via tailored core chemistry and converted into 1,2,3-triazoles through copper(I)-catalyzed click chemistry. Another key feature of this work is the development of systematic HPLC purification methods, enabling the isolation of analytically pure compounds despite structural complexity. The resulting analogs exhibit distinct antibacterial profiles, notably against Gram-positive bacteria including MRSA and Streptococcus mutans, informing structure–activity relationships and offering a foundation for further optimization. This approach supports the rapid diversification of rifamycin scaffolds to combat the escalating threat of AMR, while also establishing a foundation for future discovery through bioorthogonal applications. Full article

Refractory infections caused by multidrug-resistant bacteria have emerged as a substantial threat to public health, prompting renewed interest in phage therapy. Bacteria and phages are ubiquitous in diverse environments, engaging in continuous interaction and co-evolution. In response to phage infection, bacteria have developed an array of defense mechanisms. Current studies on bacteria–phage interactions predominantly focus on laboratory settings using artificial media, whereas the final goal of phage therapy—to combat antibiotic-resistant bacteria—lies in its clinical application. This review describes bacterial defense strategies against phage infection in the context of laboratory-based artificial media, animal experiments and clinical cases, aiming to deepen the understanding of bacteria–phage interactions and promote the advancement of effective phage therapy for clinical applications. Full article

Background: Multidrug-resistant bacteria have quadrupled globally, impacting effective treatment of infectious diseases. A growing concern is that many Gram-negative and Gram-positive bacteria harbor genes conferring resistance to various antibiotics including colistin. The alarming emergence of colistin resistance is exacerbated by the growing threat of MDR Salmonella species and Listeria monocytogenes (LMO), which pose an escalating risk to global public health. Materials and Methods: In the present study, red meat samples were collected from randomly selected key retail markets in the Eastern Cape province, South Africa, and were evaluated for the incidence of LMO and the Salmonella species using standard culture-based and molecular methods. The confirmed isolates were subjected to antibiotic susceptibility testing. Results: This study demonstrated the occurrence of multidrug-resistant LMO (62%) and Salmonella species (spp.) (58%) in the red meat specimen. There were high resistance rates in both LMO and Salmonella isolates, with LMO exhibiting resistance to penicillin (89%), colistin (81%), nitrofurantoin (78%), and erythromycin (29%), while Salmonella showed resistance to trimethoprim (96.87%), tetracycline, and colistin (90.62%). Antibiotic resistance genes were also detected including BlaTem, erm, Sul1, Sul2 and mcr 1–6. Notably, Salmonella did not harbor any mcr genes that were screened in this study, whereas Listeria isolates harbored the mcr 2 (10%), 3 (7%), 4 (10%), and 6 (3%), with mcr 5 being the most prevalent with 57%. Conclusions: These findings highlight a threat to food security and public health, emphasizing the need for sturdier food handling procedures to ensure safety, enhanced antimicrobial stewardship, and alternative therapeutic strategies to combat antibiotic-resistant pathogens. Full article

The global rise in antimicrobial resistance (AMR) demands innovative strategies beyond traditional antibiotics. Peptide Nucleic Acids (PNAs), synthetic DNA analogues with peptide-like backbones, act as thermically, chemically, and enzymatically stable sequence-specific agents capable of silencing essential bacterial genes. Through antisense mechanisms, PNAs bind bacterial mRNA or rRNA, blocking translation or ribosome assembly and thereby inducing species-specific growth inhibition. Their programmable design enables precise targeting of multidrug-resistant pathogens while sparing commensal microbiota. Recent advances, including γ-modified backbones, cationic substitutions, and delivery platforms such as cell-penetrating peptides (CPPs), dendron conjugates, and nanoparticles, have improved solubility, stability, and cellular uptake. Studies show promising in vitro and, albeit less frequently, in vivo efficacy against both Gram-positive and Gram-negative bacteria, often with synergistic activity when combined with conventional antibiotics. Although challenges remain in delivery and large-scale production, PNAs represent a promising class of antimicrobials to combat AMR through targeted gene inhibition. Full article

The therapeutic efficacy of antibiotics has been significant in extending human life expectancy by combating virulent bacterial infections. Nevertheless, multidrug-resistant (MDR) microorganisms remain a global crisis as these bacteria have developed resistance to conventional antibacterial agents. An unexplored antibiotic target found exclusively in bacteria is the Na⁺-translocating NADH:ubiquinone oxidoreductase (NQR), which is an indispensable membrane-bound bacterial enzyme complex that enables cellular functionality and is present in many infectious bacterial species, including Vibrio cholerae and H. influenzae. NQR serves as an essential complex in the bacterial electron transport chain (ETC) and operates as a highly conserved primary Na⁺ pump that drives many bioenergetic functions. This six-subunit protein shuttles electrons from NADH to ubiquinone, which drives the translocation of Na⁺ ions and creates a gradient that provides the driving force for various cellular processes. We have synthesized and evaluated a series of 1,4-naphthoquinones that exhibit high potency against NQR with minimal cytotoxicity and potential to serve as new, NQR-targeting antibacterial agents for use against V. cholerae. Full article

The global prevalence of antibiotic-resistant bacteria, such as Staphylococcus aureus, presents a substantial challenge to public health, necessitating the development of innovative therapeutic strategies to combat these infections. This study examined the synergistic effects of a biosurfactant (BS) derived from Lactiplantibacillus plantarum and a novel extract from Rosmarinus officinalis (RoME) obtained through supercritical CO₂ extraction against S. aureus sourced from the microbiology laboratory at King Salman Hospital in Ha’il, Saudi Arabia. Antibacterial efficacy was determined using minimum inhibitory concentration (MIC) assays, assessments of bacterial membrane damage, and qRT-PCR analysis of genes associated with antibiotic resistance. The findings revealed that the S. aureus strain exhibited resistance to multiple antibiotics with a resistance score of 0.44. RoME and BS demonstrated MICs of 0.125 mg/mL and 0.5 mg/mL, respectively. The assays indicated significant bacterial membrane damage and reduced expression of the norA, mdeA, and sel genes, which are implicated in resistance and virulence, respectively. The combination of BSs with plant extracts may provide innovative approaches for treating infections caused by multidrug-resistant bacteria, highlighting the potential of probiotic-derived BSs in combination with plant extracts. Full article

This review aims to systematically synthesize recent research advances on the antimicrobial peptides (AMPs) derived from the black soldier fly (Hermetia illucens). Against the backdrop of the escalating global crisis of antimicrobial resistance (AMR), AMPs have emerged as pivotal candidates to replace conventional antibiotics. As a unique saprophagous insect, H. illucens has evolved a robust and efficient innate immune system to thrive in its pathogen-rich environment. The AMPs it produces demonstrate remarkable broad-spectrum activity, high stability, and a low propensity for inducing resistance. Based on cutting-edge research available up to 2025, this article will provide an in-depth exploration of the astounding molecular diversity of H. illucens AMPs, their key structure–function relationships, and their multifaceted mechanisms of action, ranging from membrane disruption to immunomodulation. It will also highlight engineering strategies driven by artificial intelligence (AI). Finally, the review will assess the significant translational potential of these AMPs in combating multidrug-resistant bacteria, analyzing the current status of research in animal models, the challenges for industrial production, and viable future development pathways. The goal is to provide a solid theoretical foundation and forward-looking perspective to facilitate the translation of this valuable biological resource from basic research to clinical and agricultural applications. Full article