Inactivation of transcriptional regulators during withinhousehold evolution of Escherichia coli

Dagmara I. Kisiela, Matthew Radey, Sandip Paul, Stephen Porter, Kseniya Polukhina, Veronika Tchesnokova, Sofiya Shevchenko, Diana Chan, Maliha Aziz, Timothy J. Johnson, Lance B. Price, James R. Johnson, Evgeni V. Sokurenko

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5 Scopus citations

Abstract

We analyzed the within-household evolution of two household-associated Escherichia coli strains from pandemic clonal group ST131-H30, using isolates recovered from five individuals within two families, each of which had a distinct strain. Family 1's strain was represented by a urine isolate from the index patient (older sister) with recurrent cystitis and a blood isolate from her younger sister with fatal urosepsis. Family 2's strain was represented by a urine isolate from the index patient (father) with pyelonephritis and renal abscesses, blood and kidney drainage isolates from the daughter with emphysematous pyelonephritis, and urine and fecal isolates from the mother with cystitis. Collectively, the several variants of each family's strain had accumulated a total of 8 (family 1) and 39 (family 2) point mutations; no two isolates were identical. Of the 47 total mutations, 36 resulted in amino acid changes or truncation of coded proteins. Fourteen such mutations (39%) targeted genes encoding transcriptional regulators, and 9 (25%) involved DNA-binding transcription factors (TFs), which significantly exceeded the relative contribution of TF genes to the isolates' genomes (~6%). At least one-half of the transcriptional regulator mutations were inactivating, based on phenotypic and/or transcriptional analysis. In particular, inactivating mutations in the global regulator LrhA (repressor of type 1 fimbriae and flagella) occurred in the blood isolates from both households and increased the virulence of E. coli strains in a murine sepsis model. The results indicate that E. coli undergoes adaptive evolution between and/or within hosts, generating subpopulations with distinctive phenotypes and virulence potential.

Original languageEnglish (US)
Article numbere00036-17
JournalJournal of bacteriology
Volume199
Issue number13
DOIs
StatePublished - Jul 1 2017

Bibliographical note

Funding Information:
We thank Steve Moseley (University of Washington, Seattle) for critical reading of the manuscript and Brian Johnston (Veterans Affairs Medical Center, Minneapolis) and Anahit Hovhannisyan (University of Washington) for technical assistance. This work was supported by the National Institutes of Health (5R01AI106007-03 to E.V.S. and 5R21AI117654-02 to L.B.P. and J.R.J.). This material is also based in part on work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (1 I01 CX000920-01 to J.R.J.). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Keywords

  • Adaptive mutation
  • Clonal evolution
  • E. coli
  • Sepsis
  • Transcriptional regulator
  • Urinary tract infection

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