TY - JOUR

T1 - Adaptation of Escherichia coli traversing from the faecal environment to the urinary tract

AU - Nielsen, Karen L.

AU - Stegger, Marc

AU - Godfrey, Paul A.

AU - Feldgarden, Michael

AU - Andersen, Paal S.

AU - Frimodt-Moller, Niels

PY - 2016/12

Y1 - 2016/12

N2 - The majority of extraintestinal pathogenic Escherichia coli (ExPEC) causing urinary tract infections (UTI) are found in the patient’s own gut flora, but only limited knowledge is available on the potential adaptation that may occur in the bacteria in order to traverse the perineum and successfully infect the urinary tract. Here, matching pairs of faecal and UTI isolates from 42 patients were compared pairwise using in-depth whole-genome sequencing to investigate whether genetic changes were evident for successful colonization in these two different environments. The identified non-synonymous mutations (0–12 substitutions in each pair) were primarily associated to genes encoding virulence factors and nutrient metabolism; and indications of parallel evolution were observed in genes encoding the major phase-variable protein antigen 43, a toxin/antitoxin locus and haemolysin B. No differences in virulence potential were observed in a mouse UTI model for five matching faecal and UTI isolates with or without mutations in antigen 43 and haemolysin B. Variations in plasmid content were observed in only four of the 42 pairs. Although, we observed mutations in known UTI virulence genes for a few pairs, the majority showed no detectable differences with respect to mutations or mobilome when compared to their faecal counterpart. The results show that UPECs are successful in colonizing both the bladder and gut without adaptation.

AB - The majority of extraintestinal pathogenic Escherichia coli (ExPEC) causing urinary tract infections (UTI) are found in the patient’s own gut flora, but only limited knowledge is available on the potential adaptation that may occur in the bacteria in order to traverse the perineum and successfully infect the urinary tract. Here, matching pairs of faecal and UTI isolates from 42 patients were compared pairwise using in-depth whole-genome sequencing to investigate whether genetic changes were evident for successful colonization in these two different environments. The identified non-synonymous mutations (0–12 substitutions in each pair) were primarily associated to genes encoding virulence factors and nutrient metabolism; and indications of parallel evolution were observed in genes encoding the major phase-variable protein antigen 43, a toxin/antitoxin locus and haemolysin B. No differences in virulence potential were observed in a mouse UTI model for five matching faecal and UTI isolates with or without mutations in antigen 43 and haemolysin B. Variations in plasmid content were observed in only four of the 42 pairs. Although, we observed mutations in known UTI virulence genes for a few pairs, the majority showed no detectable differences with respect to mutations or mobilome when compared to their faecal counterpart. The results show that UPECs are successful in colonizing both the bladder and gut without adaptation.

KW - Urinary tract infection

KW - Whole genome sequencing

KW - Evolution

KW - Faecal flora

KW - Single-nucleotide polymorphisms

KW - Mutations

U2 - 10.1016/j.ijmm.2016.10.005

DO - 10.1016/j.ijmm.2016.10.005

M3 - Journal article

C2 - 27825516

VL - 306

SP - 595

EP - 603

JO - International Journal of Medical Microbiology

JF - International Journal of Medical Microbiology

SN - 1438-4221

IS - 8

ER -