Comparative genomics reveals the correlations of stress response genes and bacteriophages in developing antibiotic resistance of Staphylococcus saprophyticus

作者：Kailun Zhang, Robert F. Potter, Jamie Marino, Carol E. Muenks, Matthew G. Lammers, Jennifer Dien Bard, Tanis C. Dingle, Romney M. Humphries, Lars F. Westblade, Carey‐Ann D. Burnham, Gautam Dantas · 发表于：mSystems · 年份：2023 · DOI：10.1128/msystems.00697-23 · 被引用次数：10 · 研究领域：Antimicrobial Resistance in Staphylococcus、Bacteriophages and microbial interactions、Genomics and Phylogenetic Studies

ABSTRACT Staphylococcus saprophyticus is the leading Gram-positive cause of uncomplicated urinary tract infections. Recent reports of increasing antimicrobial resistance (AMR) in S. saprophyticus warrant investigation of its understudied resistance patterns. Here, we characterized a diverse collection of S. saprophyticus ( n = 275) using comparative whole genome sequencing. We performed a phylogenetic analysis of core genes (1,646) to group our S. saprophyticus and investigated the distributions of antibiotic resistance genes (ARGs). S. saprophyticus isolates belonged to two previously characterized lineages, and 14.91% (41/275) demonstrated multidrug resistance. We compared antimicrobial susceptibility phenotypes of our S. saprophyticus with the presence of different ARGs and gene alleles. 29.8% (82/275) carried staphylococcal cassette chromosome mobile elements, among which 25.6% (21/82) were mecA + . Penicillin resistance was associated with the presence of mecA or blaZ . The mecA gene could serve as a marker to infer cefoxitin and oxacillin resistance of S. saprophyticus , but the absence of this gene is not predictive of susceptibility. Utilizing computational modeling, we found several genes were associated with cefoxitin and oxacillin resistance in mecA − isolates, some of which have predicted functions in stress response and cell wall synthesis. Furthermore, phenotype association analysis indicates ARGs against non-β-lactams reported in other staphylococci may serve a...