Search Results (709)

Background/Objectives: Mycobacterium abscessus is an opportunistic pathogen causing infections mainly in patients with immunosuppression and chronic pulmonary pathologies. Extended treatment periods are needed to tackle this pathogen, bacterial eradication is rare, and recurrence can take place with time. New alternative treatments are being investigated, such as bacteriophage therapy. This work describes the characterization of the mycobacteriophage P3MA, showing its ability to infect clinical and standard M. abscessus strains. Methods: Phylogenetic analysis, electron microscopy, growth curves, biofilm assays, checkerboard, and granuloma-like medium studies were performed. Results: P3MA inhibited the growth of clinical samples in both planktonic and biofilm states as well as in a granuloma-like model. The study of the interaction with antibiotics revealed that P3MA exhibited an antagonistic effect combined with clarithromycin, indifference with amikacin, and synergy with imipenem. Conclusions: All these results suggest that, after genetic engineering, P3MA could be a promising candidate for phage therapy in combination with imipenem, including lung infections. Full article

Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at various concentrations significantly improved shrimp survival, with the 1 ppm group demonstrating the highest survival rate. Enzymatic assays revealed that phage-treated shrimp exhibited enhanced immune enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM). In addition, antioxidant defenses such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC) significantly improved, accompanied by reduced malondialdehyde (MDA) levels. Serum biochemical analyses demonstrated marked improvements in lipid metabolism, particularly reductions in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), alongside higher levels of beneficial high-density lipoprotein (HDL). Transcriptomic analysis identified 2274 differentially expressed genes (DEGs), notably enriched in pathways involving fatty acid metabolism, peroxisome functions, lysosomes, and Toll-like receptor (TLR) signaling. Specifically, phage treatment upregulated immune and metabolic regulatory genes, including Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), interleukin-1β (IL-1β), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor (PPAR), indicating activation of innate immunity and antioxidant defense pathways. These findings suggest that phage therapy induces protective immunometabolic adaptations beyond its direct antibacterial effects, thereby providing an ecologically sustainable alternative to antibiotics for managing bacterial diseases in shrimp aquaculture. Full article

Phage therapy shows promise as an adjunct to antibiotics for treating Staphylococcus aureus infections. We previously reported a combined flucloxacillin/two-phage cocktail treatment selected for resistance to podovirus phage 66 in a rodent model of methicillin-susceptible S. aureus (MSSA) endocarditis. Here we show that resistant clones harbor mutations in tarS, which encodes a glycosyltransferase essential for β-GlcNAcylation of wall teichoic acid (WTA). This WTA modification has been described in vitro as critical for podoviruses adsorption. Transcriptomics confirmed continued tarS expression in resistant clones, supporting a loss-of-function mechanism. Accordingly, phage 66 binding and killing were restored by WT tarS complementation. In addition, we investigated the counterintuitive innate susceptibility to phage 66 of the tarM + Laus102 strain used in the endocarditis model. We show that it likely results from a significant lower tarM expression, in contrast to the innate resistant strain RN4220. Our findings demonstrate that tarS-mediated WTA β-GlcNAcylation is critical for podovirus infection also in vivo and identify tarM transcriptional defect as a new mechanism of podoviruses susceptibility in S. aureus. Moreover, and since tarS disruption has been previously shown to enhance β-lactam susceptibility, our results support the development of combined podovirus/antibiotic strategies for the management of MRSA infections. Full article

The rise in antibiotic-resistant bacteria has made the management of bacterial diseases increasingly challenging. As a result, bacteriophages have gained attention as a promising alternative to antibiotics for combating bacterial pathogens. However, the usage of phages as biocontrol agents faces many challenges, including environmental stability, delivery efficiency, host specificity, and potential bacterial resistance. Advancements in genetic engineering and nanotechnology have been explored to enhance the stability, efficacy, and adaptability of phage-based treatments. In this review, we discuss the key barriers to the effective implementation of phage therapy and highlight innovative strategies to overcome these challenges. By addressing these limitations, this review aims to provide insights into optimizing phage-based approaches for widespread therapeutic and biocontrol applications. Full article

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by tissue damage in multiple organs caused by autoantibodies and the resulting immune complexes. One possible way for complement system contribution to onset of autoimmune disorder could be realized by the impairment of C1q-mediated apoptotic clearance as part of human homeostasis. The capacity of C1q to bind early apoptotic cells could be decreased or even lost in the presence of anti-C1q antibodies. A monoclonal anti-idiotypic single-chain (scFv) antibody was selected from the phage library Griffin1” to recognize anti-C1q autoantibodies, purified from sera of lupus nephritis patients. Lupus-prone MRL/lpr mice were injected weekly with scFv A1 fragment-binding anti-C1q antibodies. The number of in vitro and ex vivo studies with collected cells, sera, and organs from the treated animals was performed. scFv treatment changed the percentage of different B-, T-, and NK-cell subpopulations as well as plasma cells and plasmablasts in the spleen and bone marrow. An increase in the levels of splenocyte proliferation, anti-C1q antibodies, and the number of plasma cells producing anti-dsDNA and anti-C1q antibodies were also observed in scFv-treated animals. High levels of proteinuria and hematuria combined with unstable levels of IL10 and IFNγ promote the development of severe lupus and shorten the survival of treated MRL/lpr mice. Therapy with the scFv A1 antibody resulted in BCR recognition on the surface of anti-C1q-specific B-cells and had a disease progression effect, enhancing lupus symptoms in the MRL/lpr mouse model of SLE. Full article

Listeria monocytogenes is a life-threatening bacterial foodborne pathogen that can persist in food-processing facilities for years. Although phages can control L. monocytogenes during food production, phage-resistant bacterial subpopulations can regrow in phage-treated environments. In this study, an L. monocytogenes hly defective strain, NJ05-Δhly, was produced, which considerably regulated the interactions between L. monocytogenes and phages. Specifically, we observed a 76.92-fold decrease in the efficiency of plating of the defective strain following infection with the Listeria phage vB-LmoM-NJ05. The lytic effect was notably diminished at multiplicities of infection of 1 and 10. Furthermore, the inactivation of LLO impaired biofilm formation, which was completely suppressed and eliminated following treatment with 10⁸ PFU/mL of phage. Additionally, phages protected cells from mitochondrial membrane damage and the accumulation of mitochondrial reactive oxygen species induced by L. monocytogenes invasion. Transcriptomic analysis confirmed these findings, revealing the significant downregulation of genes associated with phage sensitivity, pathogenicity, biofilm formation, and motility in L. monocytogenes. These results underscore the vital role of LLO in regulating the pathogenicity, phage susceptibility, and biofilm formation of L. monocytogenes. These observations highlight the important role of virulence factors in phage applications and provide insights into the potential use of phages for developing biosanitizers. Full article

Antibiotic resistance presents a global threat, making the swift development of alternative treatments essential. Phage therapy, which employs bacterial viruses that specifically target bacteria, shows promise. Although this method has been utilized for over a century, primarily in Eastern Europe, its use in the US remains limited. This study aimed to assess the awareness and willingness of US healthcare providers to adopt phage therapy in response to the growing issue of antibiotic resistance. A survey of 196 healthcare providers, primarily MDs and DOs, found that while 99% were aware of antimicrobial resistance, only 49% were knowledgeable about phage therapy as a treatment for resistant bacterial infections. Nonetheless, 56% were open to considering phage therapy, and this willingness was associated with prior knowledge, concerns about antibiotic resistance, previous training, and confidence in recommending it (p < 0.05). Our study of U.S. healthcare providers revealed key findings about their views on phage therapy as a potential alternative for treating bacterial infections. Credible information is essential to promoting phage therapy use among U.S. providers via educational initiatives, clinical guidance, and research dissemination to promote phage therapy use among U.S. providers. Evidence-based education and clinical guidance help providers make sound decisions on the appropriate and safe use of phage therapy. Full article

Dairy mastitis is a common dairy farming disease. It severely affects the health of dairy cows and the quality and yield of dairy products. This paper reviews the main current mastitis treatments and associated bacterial resistance. It emphasizes the importance of integrated resistance and treatment management. The therapeutic efficacy and resistance associated with commonly used antibiotics such as penicillin, cephalosporins, macrolides and fluoroquinolones are analyzed. The principles, application effects and benefits of non-antibiotic therapies are also discussed, including those of immunotherapy, herbal therapy, probiotic therapy and phage therapy. The paper presents the latest gene editing and nanotechnology advances in the contexts of big data and artificial intelligence. It suggests future research directions such as developing new antibiotics, optimizing treatment and enhancing immunity. In conclusion, effective treatment and management can control dairy cow mastitis. It can guarantee cow health, improve dairy product quality and promote sustainable dairy industry development. Full article

Microbial infections are an escalating global health threat, driven by the alarming rise of antimicrobial resistance (AMR), which has made many conventional antibiotics increasingly ineffective and threatens to reverse decades of medical progress. The rapid emergence and spread of multidrug-resistant bacteria have severely limited treatment options, resulting in increased morbidity, mortality, and healthcare burden worldwide. In response to these challenges, phage therapy is regaining interest as a promising alternative. Bacteriophages, the most abundant biological entities, have remarkable specificity toward their bacterial hosts, enabling them to selectively eliminate pathogenic strains. Phage therapy presents several advantages over conventional antibiotics, which include minimal disruption to the microbiome and a slower rate of resistance development. Among the various sources of phages, the marine environment remains one of the least explored. Given their adaptation to saline conditions, high pressure, and variable nutrient levels, marine bacteriophages mostly exhibit enhanced environmental stability, broader host ranges, and distinct infection mechanisms, thus making them highly promising for therapeutic purposes. This review explores the growing therapeutic potential of marine bacteriophages by examining their ecological diversity, biological characteristics, infection dynamics, and practical applications in microbial disease control. It also deals with emerging strategies such as phage–antibiotic synergy, genetic engineering, and the use of phage-derived enzymes, alongside several challenges that must be addressed to enable clinical translation and regulatory approval. Advancing our understanding and application of marine phages presents a promising path in the global fight against AMR and the development of next-generation antimicrobial therapies. Full article

Canine otitis externa caused by Pseudomonas aeruginosa is a relevant disease in veterinary medicine. Given P. aeruginosa’s high priority status for the development of new antimicrobials, innovative strategies like bacteriophage therapy are essential. Lytic bacteriophages are viruses with high specificity for their bacterial hosts, making them a promising therapeutic choice in both human and veterinary medicine. This study aimed to evaluate the antimicrobial potential of bacteriophages JG005 and JG024, first characterized in terms of their biofilm-forming ability and antimicrobial susceptibility profile, against P. aeruginosa isolates obtained from dogs with otitis externa,. Bacteriophages titer, host range, and activity were assessed against P. aeruginosa biofilms via microtiter assays using crystal violet and Alamar Blue. JG024 showed lytic activity against 61.2% (n = 30/49) of the isolates, while JG005 showed lytic activity against 38.8% (n = 19/49) of the isolates. Crystal violet quantification showed that JG005 can promote strong microbial suppression of 60% (n = 6/10) and 50% (n = 5/10) of the isolates at a multiplicity of infection (MOI) of 10 and 100, respectively. JG024 presented strong microbial suppression of 20% (n = 2/10) of the isolates regardless of the MOI level tested. These phages show promising potential as an innovative treatment for canine otitis externa caused by P. aeruginosa, but further studies are needed before future clinical use. Full article

Pseudomonas aeruginosa is a major opportunistic pathogen with high levels of antibiotic resistance. Phage therapy represents a promising alternative for the treatment of difficult infections both alone and in combination with antibiotics. Here, we isolated and characterized three novel lytic myoviruses, Cisa, Nello, and Moonstruck. Genomic analysis revealed that Cisa and Nello belong to the Pbunavirus genus, while Moonstruck is a novel Pakpunavirus species. All lacked lysogeny, virulence, or resistance-associated genes, supporting their therapeutic suitability. Phage Nello and Moonstruck were active against P. aeruginosa Pa3GrPv, isolated from a patient with lung infection candidate for phage therapy. Moonstruck exhibited superior lytic activity with ciprofloxacin sub-MIC value (0.125 µg/mL), achieving bacterial suppression for 48 h. However, to improve the lytic efficacy of the phages on the clinical isolate, phage adaptation via serial passage was investigated. The killing efficacy of Nello was enhanced, whereas Moonstruck showed a less consistent improvement, suggesting phage-specific differences in evolutionary dynamics. Sequencing of the evolved phages revealed point mutations in tail-associated genes, potentially linked to a better phage–host interaction. These results support the use of phage–antibiotic combinations and directed evolution as strategies to enhance phage efficacy against drug-resistant infections. Overall, these findings support the therapeutic potential of the newly isolated phages in treating P. aeruginosa lung infections. Full article

The global rise of carbapenem-resistant Acinetobacter baumannii (CRAB) strains poses a critical challenge to healthcare systems due to limited therapeutic options and high mortality rates, especially in intensive care settings. This review explores the epidemiological landscape and molecular mechanisms driving carbapenem resistance, including the production of diverse beta-lactamases (particularly OXA-type enzymes), porin loss, efflux pump overexpression, and mutations in antibiotic targets. Emerging treatment strategies are discussed, such as the use of new beta-lactam–beta-lactamase inhibitor combinations (e.g., sulbactam–durlobactam), siderophore cephalosporins, next-generation polymyxins, as well as novel agents like zosurabalpin and rifabutin (BV100). Alternative approaches—including phage therapy, antimicrobial peptides, CRISPR-based gene editing, and nanoparticle-based delivery systems—are also evaluated for their potential to bypass traditional resistance mechanisms. Furthermore, advances in artificial intelligence and multi-omics integration are highlighted as tools for identifying novel drug targets and predicting resistance profiles. Together, these innovations represent a multifaceted strategy to overcome CRAB infections, yet their successful implementation requires further clinical validation and coordinated surveillance efforts. This analysis highlights the urgent need for continued investment in innovative treatments and effective resistance monitoring to limit the spread of CRAB and protect the effectiveness of last-line antibiotics. Full article

The increasing prevalence of multidrug-resistant (MDR) bacterial infections necessitates the exploration of alternative antimicrobial strategies, with phage therapy emerging as a viable option. However, the effectiveness of naturally occurring phages can be significantly limited by bacterial defense systems that include adsorption blocking, restriction–modification, CRISPR-Cas immunity, abortive infection, and NAD+ depletion defense systems. This review examines these bacterial defenses and their implications for phage therapy, while highlighting the potential of phages’ bioengineering to overcome these barriers. By leveraging synthetic biology, genetically engineered phages can be tailored to evade bacterial immunity through such modifications as receptor-binding protein engineering, anti-CRISPR gene incorporation, methylation pattern alterations, and enzymatic degradation of bacterial protective barriers. “Armed phages”, enhanced with antimicrobial peptides, CRISPR-based genome-editing tools, or immune-modulating factors, offer a novel therapeutic avenue. Clinical trials of bioengineered phages, currently SNIPR001 and LBP-EC01, showcase their potential to safely and effectively combat MDR infections. SNIPR001 has completed a Phase I clinical trial evaluating safety in healthy volunteers, while LBP-EC01 is in Phase II trials assessing its performance in the treatment of Escherichia coli-induced urinary tract infections in patients with a history of drug-resistant infections. As “armed phages” progress toward clinical application, they hold great promise for precision-targeted antimicrobial therapies and represent a critical innovation in addressing the global antibiotic resistance crisis. Full article

Multidrug-resistant (MDR) bacterial infections present a major challenge in cancer therapy, particularly for immunocompromised patients undergoing chemotherapy, radiation, or surgery. These infections often arise from prolonged antibiotic use, hospital-acquired pathogens, and weakened immune defenses, leading to increased morbidity and mortality. As conventional antibiotics become less effective against MDR strains, there is an urgent need for alternative treatment options. This review highlights phage therapy as a promising approach to managing MDR bacterial infections in cancer patients. Once widely used, phage therapy has recently regained attention as a targeted antimicrobial strategy that can specifically eliminate harmful bacteria while preserving the beneficial microbiota. Phages work by directly lysing bacteria, disrupting biofilms, and synergizing with antibiotics to restore bacterial susceptibility. These mechanisms make phage therapy especially appealing for treating infections that complicate cancer treatments. However, the clinical application of phage therapy faces challenges such as variability in phage–host interactions, regulatory hurdles, and immune responses in patients. This review identifies gaps in current research regarding the use of phage therapy for MDR infections in cancer patients. By examining recent innovations, therapeutic mechanisms, and associated limitations, we provide valuable insights into the potential of phage therapy for improving infection management in oncology. Future research should focus on refining phage delivery methods, assessing long-term safety, and exploring combination therapies to maximize clinical efficacy. Overcoming these challenges could position phage therapy as a valuable complement to existing antimicrobial strategies in cancer care. Full article

Background: Multidrug-resistant (MDR) Escherichia coli (E. coli) strains pose a significant public health challenge, which has led to the exploration of alternative therapeutic strategies. Due to their antibacterial and immunomodulatory properties, bacteriophages have emerged as promising therapeutic agents. Methods: This study investigates the effects of GADS24, a novel lytic bacteriophage of E. coli, on human-monocyte-derived dendritic cells (DCs). DCs are exposed to purified GADS24 phage, bacterial lysate, or a combination of both. Flow cytometry was used to assess the expression of surface markers (HLA-DR, CD80, CD83, and CD86), and ELISA was used to measure cytokine production (IL-10 and IL-12p70). Results: Following treatment with bacterial lysate, a significant increase in DC maturation markers was observed. The GADS24 phage alone induced a moderate upregulation of these markers, decreased IL-10 secretion, and increased IL-12p70. Combining bacterial lysate and phage tempered the maturation response compared to the lysate treatment alone. Conclusion: These findings suggest that GADS24 exerts antibacterial activity and modulates host immunity by influencing DC maturation and cytokine production. Due to its dual antimicrobial and immunomodulatory functions, GADS24 is likely to be a valuable adjunctive therapy for multidrug-resistant (MDR) bacterial infections. Furthermore, in vivo studies are necessary to confirm these promising in vitro results. Full article