Within-host Diversity of Multidrug-Resistant Escherichia coli in the Gut and Bladder

Abstract

Uropathogenic E. coli are paradoxically able to both cause disease in the urinary tract, and reside there asymptomatically. The pandemic, multi-drug resistant E. coli subclone ST131-H30 (H30) is of special interest, as it has been found to persist in the gut and bladder of healthy people. In order to understand this persistence, we investigated whether H30 is competitive in these niches and thus able to persist by excluding other E. coli, as well as whether H30 may persist via within-host adaptation. In order to assess the E. coli clonal landscape, we developed a novel method based on deep sequencing of two loci, along with an algorithm for analysis of resulting data. Using this method, we assessed fecal and urinary samples from healthy women carrying H30, and found that even in the absence of antibiotic use, H30 could completely dominate the gut and, especially, urine of healthy carriers. In order to ascertain whether H30 adapts within host, we employed population-level whole genome sequencing, and determined that H30 undergoes changes in genes affecting respiration in the gut, similar to commensal gut E. coli. Furthermore, we find that in the bladder, H30 undergoes changes potentially adaptive for growth in urine, including nonsynonymous mutations in iron and amino acid metabolism genes.