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J. Bacteriol. doi:10.1128/JB.01696-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Genetic analysis of Helicobacter pylori strain populations colonizing the stomach at different times post-infection

Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Microbiology, University of Washington School of Medicine, Seattle, WA; Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatria, IMSS, Mexico; Wolfson Digestive Diseases Centre and Institute of Infection, Immunity and Inflammation, University of Nottingham, UK; Department of Medicine/Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX

^* To whom correspondence should be addressed. Email: nsalama{at}fhcrc.org.

	Abstract

Genetic diversity of the human gastric pathogen Helicobacter pylori within an individual host has been observed; whether this represents diversification of a founding strain or mixed infection by distinct strain populations is not clear. To explore this issue we analyzed multiple single colony isolates from 2-4 separate stomach biopsies of eight adult and four pediatric patients from a high incidence Mexican population. Eleven of twelve patients contained isolates with identical RAPD, AFLP, and vacA allele molecular footprints, whereas a single adult patient had two distinct profiles. Comparative genomic hybridization using whole genome microarrays (array CGH) revealed variation in 24-67 genes in isolates from patients with similar molecular footprints. One patient with distinct patterns had two strain populations differing at 113 gene loci including the cag PAI virulence genes. The two strain populations in this single host displayed different spatial distributions within the stomach and very limited genetic exchange. The total and pair-wise genetic divergence between isolates from adults and children was not statistically different. We also analyzed isolates obtained 15 and 90 days after experimental human infection and found no evidence of genetic divergence indicating that transmission to a new host does not induce rapid genetic changes in the bacterial population within the human stomach. Our data suggest humans are infected with a population of highly related strains varying in a small number of gene loci, this population of strains may already be present during acquisition of infection and even upon super-infection genetic exchange among distinct strains is rare.