Two novel trimethoprim resistance genes, dfra50 and dfra51 , identified in phage-plasmids

作者：Kai Wang, J. Xu, Xiao-Ming Lu, Pan Yin, Li Chen, Ziwei Zhao, Alejandra Bravo, Mário Soberón, Jinshui Zheng, Ming Sun, Donghai Peng · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2025 · DOI：10.1128/aac.01695-24 · 被引用次数：4 · 研究领域：Bacteriophages and microbial interactions、Antibiotic Resistance in Bacteria、Pneumocystis jirovecii pneumonia detection and treatment

ABSTRACT Phage-plasmids carry a significant burden of clinically relevant antibiotic resistance genes (ARGs). Intriguingly, the majority of these ARGs are found within plasmids with phage features, with a single exception residing in a phage genome with plasmid features. Therefore, we speculate that phage genomes with plasmid features, whose sequences are highly homologous to bacterial plasmids, may carry novel ARGs. We subsequently identified 46 such phage genomes by employing Hidden Markov models (HMMs) based on plasmid-specific protein profiles andbasic local alignment search tool (BLASTn) searches against the National Center for Biotechnology Information (NCBI) RefSeq Plasmid Database. Among them, six phages harbored seven ARGs identified through a lenient-threshold search strategy, of which only two had been previously reported. The remaining five ARGs were categorized as novel ARGs since their encoded proteins differed from known ARGs. Notably, half of the phages carried trimethoprim-resistant dfrA -like genes. Functional studies characterized these genes and demonstrated that the expression of two of these dfrA genes ( dfrA50 and dfrA51 ) can confer resistance to trimethoprim in Escherichia coli . Through genome analysis, we found that these phages with plasmid features likely contributed to the natural dissemination of these dfrA genes, as evidenced by their widespread presence in plasmids across various pathogenic bacteria. These findings underscore the importance of...