Arrangements of Mobile Genetic Elements among Virotype E Subpopulation of Escherichia coli Sequence Type 131 Strains with High Antimicrobial Resistance and Virulence Gene Content

Escherichia coli sequence type 131 (ST131) is known for its contribution to multidrug resistance and the worldwide spread of this clone has become a global problem. Understanding the trends among ST131 clades will help design strategies to prevent its rapid dissemination. In this study, 72 ST131 strains were subjected to comparative genomic analysis and 64 clade C strains were compared with clade C strains reported from other regions using publicly available whole-genome sequencing data. C1 (n = 31 [48.4%]) and C2 (n = 33 [%51.5]) strains had the same prevalence in our collection, and C1-M27 (n = 22) strains were closely related, carried a unique plasmid type (F1:A2:B20), and exhibited virotype C. Removal of 11 C2 strains with varied virotype patterns and the heterogeneous IncF type identified 22 closely related virotype E/F strains with replicon type F31/F36:A4:B1, forming what we denote as the “C2-subset.” In a global context, the C2-subset constituted a distinct cluster with international virotype E strains and harbored a genomic island, GI-pheU. Association of cnf1/hlyCABD genes with 1 to 7 mobile genetic elements, mostly IS682/ISKpn37 combination within GI-pheU was identified. The C2-subset accounted for excess resistance/virulence of subclade C2 relative to C1 strains. In addition, a conserved chromosomal IS26-mediated composite transposon (IS15DIV-ISEcp1-bla(CTX-M-15)-WbuC cupin fold metalloprotein-Tn2-IS15DIV) was observed in the C2-subset. The local spread of the C2-subset in the hospital studied, with the carriage of higher virulence/resistance markers and a peculiar F-type plasmid, demonstrates the potential for diversification of the ST131 lineage and the emergence of subpopulations with higher survival potential to cause health care-associated outbreaks. IMPORTANCEEscherichia coli sequence type 131 (ST131) is a globally dominant multidrug-resistant clone that is commonly associated with extraintestinal infections. Specific sublineages have been shown to have emerged and spread within ST131, highlighting the complex nature of ST131 epidemiology. This study systematically compared the Iranian ST131 population to those reported from other countries and found a subpopulation harboring virotype E, a homogeneous profile of plasmid Inc-F type F31/F36:A4:B1 harboring cnf1/hemolysin genes on the genomic island GI-pheU, and up to seven mobile genetic elements (MGEs) flanking cnf1/hemolysin virulence markers. The results of this study highlight the importance of MGEs for virulence gene acquisition and the formation of new subpopulations among pandemic clones such as E. coli ST131.