Genomic and In Vivo Characterization of Antimicrobial Resistance and Virulence in UPEC Escherichia coli Isolated from Brazilian Cases of UTI

从巴西尿路感染病例中分离的泌尿道致病性大肠杆菌的抗菌素耐药性和毒力的基因组学和体内特征分析

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Abstract

With the growing global prevalence of antimicrobial resistance, the treatment of urinary tract infections caused by Escherichia coli is becoming increasingly challenging. Uropathogenic E. coli (UPEC) is responsible for approximately 80% of urinary infections worldwide and possesses extraordinary genetic plasticity that facilitates both antimicrobial resistance and virulence. This study aimed to characterize the genomic profiles of four clinical UPEC strains (SJR07, SJR30, SJR31, and SJR49) that were recently isolated from women with UTIs in the city of Divinópolis, Brazil. Through whole-genome sequencing and comparative analysis, we identified a high degree of genetic diversity, including a heterogeneous repertoire of resistance and virulence genes located on plasmids and genomic islands. In particular, the extended spectrum beta-lactamase (ESBL) gene SHV-12 variant was found in a mobilizable plasmid in the genome of the SJR49 strain. Notably, phylogenetic and sequence-type (ST) analyses revealed the presence of globally relevant lineages such as ST10 and ST354, which are known for their adaptability and resistance potential. Functional assays using an experimental renal infection model demonstrated the ability of SJR49 to persist in the renal tissue and induce more severe functional and histopathological kidney damage. These findings highlight the urgent need to develop therapeutic strategies for community-acquired UPEC infections and mitigate the spread of multidrug-resistant strains.

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