Conserved FimH mutations in the global Escherichia coli ST131 multi-drug resistant lineage weaken interdomain interactions and alter adhesin function.

ABSTRACT: The binding of the type 1 fimbrial adhesin FimH to mannosylated receptors is allosterically regulated to enhance the fitness of uropathogenic Escherichia coli (UPEC) during urinary tract infection (UTI). Mutations in the two FimH domains (pilin and lectin) located outside the mannose binding pocket have been shown to influence mannose binding affinity, yet the details of the allostery mechanism are not fully elucidated. Here we characterised different FimH conformational states (termed low-affinity tense and high-affinity relaxed conformations) of natural FimH variants using molecular dynamics (MD) simulation techniques and report key structural dynamics differences between them. The clinically dominant FimH30 variant from the pandemic multidrug resistant E. coli ST131 lineag

SUBMITTER: Qin J 

PROVIDER: S-EPMC9428848 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature