A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug resistant uropathogenic <em>Escherichia coli</em> ST131 — ASN Events
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  2. Division 4 – Microbial Genetics, Physiology and Pathogenesis
  3. Symposium 6 - The Varied Roles of Bacterial Surface Structures: Biofilms and More
  4. A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug resistant uropathogenic Escherichia coli ST131

A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug resistant uropathogenic Escherichia coli ST131 (#130)

Makrina Totsika 1 , Maria Kostakioti 2 , Thomas J Hannan 2 , Mathew Upton 3 , Scott A Beatson 1 , James W Janetka 2 , Scott J Hultgren 2 , Mark A Schembri 1
  1. University of Queensland, Brisbane, QLD, Australia
  2. Washington University School of Medicine, St. Louis, MO, USA
  3. University of Manchester, Manchester, United Kingdom

Background. Escherichia coli O25b:H4-ST131 represent a predominant clone of multidrug resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTI) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent.

Methods. Using established mouse models of acute and chronic UTI we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958.

Results. We demonstrated that E. coli EC958 can invade into bladder epithelial cells and form intracellular bacterial communities (biofilms) early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration failed to prevent E. coli EC958 mediated UTI. However, one oral dose of a small molecular weight compound that inhibits FimH, the type 1 fimbriae adhesin, significantly reduced bacterial colonization of the bladder and prevented acute UTI. Treatment of chronically infected mice with the same FimH inhibitor lowered their bladder bacterial burden by more than 1000-fold.

Conclusions. In this study, we provide novel insight into the pathogenic mechanisms employed by the globally disseminated E. coli ST131 clone during acute and chronic UTI and establish the potential of FimH inhibitors as an alternative treatment against multidrug resistant E. coli.