Redefining enteroaggregative escherichia coli (Eaec): Genomic characterization of epidemiological eaec strains

Nadia Boisen*, Mark T. Østerlund, Katrine G. Joensen, Araceli E. Santiago, Inacio Mandomando, Alejandro Cravioto, Marie Anne Chattaway, Laura A. Gonyar, Søren Overballe-Petersen, O. Colin Stine, David A. Rasko, Flemming Scheutz, James P. Nataro

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
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Abstract

Although enteroaggregative E. coli (EAEC) has been implicated as a common cause of diarrhea in multiple settings, neither its essential genomic nature nor its role as an enteric pathogen are fully understood. The current definition of this pathotype requires demonstration of cellular adherence; a working molecular definition encompasses E. coli which do not harbor the heat-stable or heat-labile toxins of enterotoxigenic E. coli (ETEC) and harbor the genes aaiC, aggR, and/or aatA. In an effort to improve the definition of this pathotype, we report the most definitive characterization of the pan-genome of EAEC to date, applying comparative genomics and functional characterization on a collection of 97 EAEC strains isolated in the course of a multicenter case-control diarrhea study (Global Enteric Multi-Center Study, GEMS). Genomic analysis revealed that the EAEC strains mapped to all phylogenomic groups of E. coli. Circa 70% of strains harbored one of the five described AAF variants; there were no additional AAF variants identified, and strains that lacked an identifiable AAF generally did not have an otherwise complete AggR regulon. An exception was strains that harbored an ETEC colonization factor (CF) CS22, like AAF a member of the chaperone-usher family of adhesins, but not phylogenetically related to the AAF family. Of all genes scored, sepA yielded the strongest association with diarrhea (P = 0.002) followed by the increased serum survival gene, iss (p = 0.026), and the outer membrane protease gene ompT (p = 0.046). Notably, the EAEC genomes harbored several genes characteristically associated with other E. coli pathotypes. Our data suggest that a molecular definition of EAEC could comprise E. coli strains harboring AggR and a complete AAF(I-V) or CS22 gene cluster. Further, it is possible that strains meeting this definition could be both enteric bacteria and urinary/systemic pathogens.

Original languageEnglish
Article numbere0008613
Pages (from-to)1-19
Number of pages19
JournalPLoS Neglected Tropical Diseases
Volume14
Issue number9
DOIs
Publication statusPublished - 8 Sep 2020

Bibliographical note

Funding Information: This study was supported by DFF1333-00156 to N.B.O and The National Institutes of Health grants AI-033096 and AI-125181 to J. P. N. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Open Access: This is an open access article distributed under the terms of the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publisher Copyright: © 2020 Boisen et al.

Citation: Boisen N, Østerlund MT, Joensen KG, Santiago AE, Mandomando I, Cravioto A, et al. (2020) Redefining enteroaggregative Escherichia coli (EAEC): Genomic characterization of epidemiological EAEC strains. PLoS Negl Trop Dis
14(9): e0008613.

DOI: https://doi.org/10.1371/journal.pntd.0008613

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