Natural Competence Promotes Helicobacter pylori Chronic Infection.

Division of Human Biology, Fred Hutchinson Cancer Research Center. 1100 Fairview Ave. N, Seattle, WA 98109.
Infection and immunity (Impact Factor: 4.16). 10/2012; DOI: 10.1128/IAI.01042-12
Source: PubMed

ABSTRACT Animal models are important tools for studies of human disease, but developing these models is a particular challenge for organisms with restricted host ranges, such as the human stomach pathogen Helicobacter pylori. In most cases, H. pylori infects the stomach for many decades before symptoms appear, distinguishing it from many bacterial pathogens that cause acute infection. To model chronic infection in the mouse, a human clinical isolate was selected for its ability to survive for two months in the mouse stomach and the resulting strain, MSD132, colonized the mouse stomach for at least 28 weeks. During selection, the cagY component of the Cag type-IV secretion system was mutated, disrupting a key interaction with host cells. Increases in both bacterial persistence and bacterial burden occurred prior to this mutation and a mixed population of cagY+ and cagY- cells was isolated from a single mouse, suggesting that mutations accumulate during selection and that factors in addition to the Cag apparatus are important for murine adaptation. Diversity in both alleles and genes is common in H. pylori strains and natural competence mediates a high rate of inter-strain genetic exchange. Mutants of the Com apparatus, a membrane DNA transporter, and DprA, a cytosolic competence factor, showed reduced persistence, although initial colonization was normal. Thus, exchange of DNA between genetically heterogeneous H. pylori may improve chronic colonization. The strains and methods described here will be important tools for defining both the spectrum of mutations that promote murine adaptation and the genetic program of chronic infection.

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    ABSTRACT: The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host-pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
    Nucleic Acids Research 12/2014; 43(1). DOI:10.1093/nar/gku1271 · 8.81 Impact Factor

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