International Journal of Antimicrobial Agents最新文献

Background: Quinolone-resistant Shigella has emerged as a significant global public health challenge.

Methods: We assembled a global collection of 8325 plasmid-mediated quinolone resistance (PMQR)-positive Shigella isolates (1998-2025) and subjected them to comprehensive genomic analysis.

Results: Geographically, the isolates spanned 37 countries, with the majority sourced from the United States (47.02%) and United Kingdom (32.28%). Eight distinct PMQR genes-aac(6')-Ib-cr, oqxAB, qepA, qnrA, qnrB, qnrD, qnrS, and qnrVC-were identified in the Shigella analyzed. qnrS was the most predominant PMQR gene (62.05%), followed by qnrB (38.76%). One hundred and eight sequence types (STs) were identified among the PMQR-positive Shigella isolates, with ST152 predominating (59.51%). Notably, multiple antibiotic resistance genes (ARGs) were universal in PMQR-positive Shigella, with aph(6)-Id (5825/8325), tet(B) (2398/8325), and blaTEM-1 (2232/8325) most prevalent. PMQR-positive Shigella from developed countries displayed a significant decreasing trend in ARGs abundance as collection year and the opposite trend in the abundance of virulence factors (VFs) between developed and developing countries (P < 0.001). Correlation analysis demonstrated the mobile genetic elements constitute principal vectors for PMQR genes spread. Plasmid replicons abundance positively correlated with ARGs abundance (P < 0.001), demonstrating plasmid-driven ARGs spread in PMQR-positive Shigella. In addition, high genetic similarity among geographically dispersed PMQR-positive Shigella isolates implies intercountry dissemination.

Conclusions: These findings elucidate PMQR-positive Shigella genomic characteristics and transmission dynamics, necessitating global surveillance reinforcement against this antimicrobial resistance threat.

The increasing prevalence of antibiotic-resistant Salmonella Typhimurium has highlighted the urgent need for alternative therapeutic strategies. This study evaluated the antibacterial efficacy of a genetically engineered bacteriophage displaying the antimicrobial peptide, LL37, against S. Typhimurium. Despite displaying LL-37 in the virion structure, the engineered-phage exhibited thermal and pH stabilities comparable to those of the wild-type phage. Notably, it demonstrated enhanced antibacterial activity, primarily owing to an increased adsorption rate. In a cell lysis assay, the engineered-phage sustained bacterial suppression for 24-72 h, whereas the wild-type phage allowed bacterial regrowth, owing to the emergence of phage-resistant mutants. In epithelial cell interaction assays, the engineered-phage significantly reduced bacterial attachment and internalization compared with its wild-type counterpart. Furthermore, intracellular survival assays revealed that the engineered-phage effectively reduced bacterial persistence in host cells. In an in vivo prophylactic assay, the engineered-phage significantly improved larval survival in a Galleria mellonella infection model in a dose-dependent manner, providing protection equivalent to 100 times that of the wild-type phage. Notably, no significant cytotoxicity was observed at either the cellular or animal levels, supporting the safety and therapeutic potential of the engineered-phage. These findings highlight phage engineering as a promising strategy for enhancing antibacterial efficacy and combating antibiotic-resistant bacterial infections.