Genomic diversity of EPEC associated with clinical presentations of differing severity.

Tracy H. Hazen
Michael S. Donnenberg
Sandra Panchalingam
Martin Antonio
Anowar Hossain
Inacio Mandomando
John Benjamin Ochieng
Thandavarayan Ramamurthy
Boubou Tamboura
Shahida Qureshi, Aga Khan University
Farheen Quadri
Anita Zaidi, Agha Khan University
Karen L. Kotloff
Myron M. Levine
Eileen M. Barry
James B. Kaper
David A. Rasko
James P. Nataro

Abstract

Enteropathogenic Escherichia coli (EPEC) are diarrhoeagenic E. coli, and are a significant cause of gastrointestinal illness among young children in developing countries. Typical EPEC are identified by the presence of the bundle-forming pilus encoded by a virulence plasmid, which has been linked to an increased severity of illness, while atypical EPEC lack this feature. Comparative genomics of 70 total EPEC from lethal (LI), non-lethal symptomatic (NSI) or asymptomatic (AI) cases of diarrhoeal illness in children enrolled in the Global Enteric Multicenter Study was used to investigate the genomic differences in EPEC isolates obtained from individuals with various clinical outcomes. A comparison of the genomes of isolates from different clinical outcomes identified genes that were significantly more prevalent in EPEC isolates of symptomatic and lethal outcomes than in EPEC isolates of asymptomatic outcomes. These EPEC isolates exhibited previously unappreciated phylogenomic diversity and combinations of virulence factors. These comparative results highlight the diversity of the pathogen, as well as the complexity of the EPEC virulence factor repertoire.