The Escherichia coli ST131 clone has emerged as the leading cause of multidrug resistant urinary tract and bloodstream infections worldwide. To date, the virulence mechanisms defining its pathogenesis remain to be properly evaluated.
The type 1 fimbria (T1F) is an important phase-variable host colonization factor. We detected the presence of T1F in 97.8% of our E. coli ST131 collection (n=91) by PCR. Functional expression of T1F was a critical determinant of in vitro biofilm formation and bladder colonization in a mouse model of urinary tract infection (UTI). However, analysis of metagenomics data from urine samples of eight individuals with acute UTI showed that T1F expression was primarily turned ‘off’ (>95% in each sample). The FimB and FimE tyrosine recombinases are known to regulate the phase variability of fimbrial expression. A significant proportion (63%) of the strains in our collection contains an insertion element within the fimB regulatory gene (fimB::ISEc55) resulting in reduced T1F expression. We found that strains with the fimB::ISEc55 insertion have several conserved nucleotide changes within the promoter region of fimE (usually turns the fim switch, fimS, ‘off’) and almost six-fold higher expression compared to strains with an intact fimB. Here we have demonstrated that in the representative ST131 strain EC958, fimE and fimX (a distally located tyrosine recombinase) regulate switching ‘on’ of T1F expression. Transposon mutagenesis of fimE and fimX promoter-lacZ reporter strains revealed that the (p)ppGpp regulatory alarmone and intracellular GTP concentrations mediate the regulation of T1F expression by altering the activity of the fimE and fimX promoters. Overall, these results shed light on the altered regulation of T1F expression in a clinically predominant sub-group of the E. coli ST131 clonal lineage and demonstrate its importance in its pathogenesis. Novel antimicrobials targeting T1F are currently under investigation and our findings will greatly aid in their development.