Genotype dependence of virulence-associated genes in ESBL-producing Escherichia coli isolated from the blood of patients with urinary tract infections

Abstract

Approximately 80% of urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC). The prevalence of extended-spectrum {beta}-lactamase (ESBL)- producing E. coli in UPEC isolates belonging to specific multilocus sequence-type clones is a global concern. Relations between the pathogenicity of UPEC virulence factors and genotype have been discussed. However, the specific virulence factors and genotypes associated with a higher likelihood of causing UTIs remain unclear. This study analyzed the genotypes and virulence-associated genes of 46 ESBL-producing strains isolated from the blood of patients with UTIs who visited the Department of Emergency Medicine from 2017 to 2022 to elucidate the characteristics of UPEC strains associated with severe infections. Most phylogroups of clinical isolates were B2, except for D, found in three strains. The dominant multilocus sequence typing (MLST) was ST131, followed by ST73, ST95, and ST38, frequently observed in UPEC strains. ST131 strains were more resistant to levofloxacin (87.5%) than non-ST131 strains (50.0%) and caused fewer sepsis cases than non-ST131 strains. Based on in silico analysis, of 23 clinical isolates, the genes detected in all clinical strains could have important role in invasive UTIs. Clustering analysis highlighted the genotype MLST dependence of UPEC-specific virulence-associated genes. The absence of several UPEC-specific gene loci or the presence of ST38-specific indicated atypical repertories of virulence-associated genes in ST38 strains. Genes encoding secretion systems, which were found in enteropathogenic E. coli, were less detected in ST131 strains. These results suggested that the correlation of MLST and repertories should be considered to understand UPEC virulence. IMPORTANCE STATEMENTSeveral virulence genes, their diverse repertories depending on the strains, and various pathological indications complicate the pathogenicity of uropathogenic Escherichia coli (UPEC). The genes detected in all clinical isolates in this study would play a crucial role in UPEC pathogenicity. In contrast, depending on the genotype, the distribution of UPEC- specific genes and other pathogenic E. coli virulence genes in some genotype strains varied. Secretion system genes related to the pathogenicity of enteropathogenic E. coli (EPEC) were less in the strains of the most prevalent genotype, ST131; this was relevant to the number of sepsis cases. These results clearly indicated genotype dependencies on virulence-associated gene repertories and ambiguity in UPEC and EPEC. This study proposed that analyzing genotype-specific virulence factors and sharing virulence genes with EPEC will bring new insights into UPEC pathogenicity.