Abstract
Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.
Highlights
Clonal dissemination of uropathogenic Escherichia coli (UPEC) occurs much more often than is commonly realized [1]
Strain EC958 was selected as a representative of the ST131 CTX-M-15 producing lineage circulating in the region as it was recovered from a urine sample of a patient presenting in the community with urinary tract infection (UTI), was gentamicin susceptible, resistant to ciprofloxacin, produced CTXM-15 extended spectrum b-lactamases (ESBLs) and carried the CMY-23 type AmpC cephalosporinase [16]
The rapid and widespread dissemination of multiply antibiotic resistant UPEC strains from the ST131 lineage in hospitals and the community represents a serious threat to healthcare resources worldwide
Summary
Clonal dissemination of uropathogenic Escherichia coli (UPEC) occurs much more often than is commonly realized [1]. Within the last five years, E. coli clone O25:H4-ST131 (E. coli ST131) has emerged as an important multi-drug resistant extraintestinal pathogen worldwide. E. coli ST131 are major contributors to what is known as ‘the CTX-M pandemic’; a recent worldwide increase in E. coli uropathogens that produce CTX-M type type (‘active on CefoTaXime, first isolated in Munich’) extended spectrum b-lactamases (ESBLs) [9]. E. coli ST131 are commonly identified among E. coli producing CTX-M-15; currently the most widespread CTX-M ESBL enzyme worldwide [7,10]. E. coli ST131 is frequently resistant to fluoroquinolones [6,11]. This clone is typically associated with limited treatment options
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