Comprehensive analysis of type 1 fimbriae regulation in fimB -null strains from the multidrug resistant Escherichia coli ST131 clone
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2016-09-06Author
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<jats:title>Summary</jats:title><jats:p>Uropathogenic <jats:italic>Escherichia coli</jats:italic> (UPEC) of sequence type 131 (ST131) are a pandemic multidrug resistant clone associated with urinary tract and bloodstream infections. Type 1 fimbriae, a major UPEC virulence factor, are essential for ST131 bladder colonization. The globally dominant sub‐lineage of ST131 strains, clade C/<jats:italic>H</jats:italic>30‐R, possess an IS<jats:italic>Ec55</jats:italic> insertion in the <jats:italic>fimB</jats:italic> gene that controls phase‐variable type 1 fimbriae expression via the invertible <jats:italic>fimS</jats:italic> promoter. We report that inactivation of <jats:italic>fimB</jats:italic> in these strains causes altered regulation of type 1 fimbriae expression. Using a novel read‐mapping approach based on Illumina sequencing, we demonstrate that ‘off’ to ‘on’ <jats:italic>fimS</jats:italic> inversion is reduced in these strains and controlled by recombinases encoded by the <jats:italic>fimE</jats:italic> and <jats:italic>fimX</jats:italic> genes. Unlike typical UPEC strains, the nucleoid‐associated H‐NS protein does not strongly repress <jats:italic>fimE</jats:italic> transcription in clade C ST131 strains. Using a genetic screen to identify novel regulators of <jats:italic>fimE</jats:italic> and <jats:italic>fimX</jats:italic> in the clade C ST131 strain EC958, we defined a new role for the <jats:italic>guaB</jats:italic> gene in the regulation of type 1 fimbriae and in colonisation of the mouse bladder. Our results provide a comprehensive analysis of type 1 fimbriae regulation in ST131, and highlight important differences in its control compared to non‐ST131 UPEC.</jats:p>
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