Genomic characterization and comparative analysis of multidrug-resistant uropathogenic Escherichia coli strain U1...

Uropathogenic Escherichia coli (UPEC) is a primary etiological agent of urinary tract infections (UTIs) worldwide. The emergence of multidrug-resistant (MDR) UPEC strains, especially the globally disseminated ST131 clone, poses a critical health threat in regions like Pakistan, where comprehensive genomic data is limited. This study performed an in-depth genomic characterization of a newly isolated MDR UPEC strain (U1) and conducted a comparative pangenome analysis of 73 UPEC genomes from Pakistan. The overall cohort exhibited an average genome size of 5.2 Mb, an average GC content of 50.6%, and an average of 5180 coding sequences. In silico genomic analysis identified U1 as a high-risk ST131 lineage member (O25:H4, phylogroup B2). The strain exhibited an MDR profile, supported by the prediction of key antibiotic resistance genes (ARGs), including bla^CTX-M-15 and dfrA17, as well as several putative virulence factors (VFs) and four plasmid replicon types. The comparative analysis revealed a highly diverse and open pangenome (3280 core and 10,977 unique genes). The U1 genome's total coding sequences (5273 genes) contribute ~ 30% share of the total pangenome gene families, indicating its status as a well-equipped strain with essential genes (core) and a substantial number of fitness and adaptability genes (accessory/unique). Core-genome phylogeny confirmed the prevalence of the ST131 lineage, with U1 clustering closely with other local isolates. Widespread VFs and ARGs highlight their critical role in UPEC adaptability. These findings demand urgent antimicrobial stewardship and enhanced genomic surveillance to control the spread of MDR UPEC, particularly the ST131 clone, in Pakistan.