Genetic signatures for Helicobacter pylori strains of West African origin

PLOS ONE, Nov 2017

Helicobacter pylori is a genetically diverse bacterial species that colonizes the stomach in about half of the human population. Most persons colonized by H. pylori remain asymptomatic, but the presence of this organism is a risk factor for gastric cancer. Multiple populations and subpopulations of H. pylori with distinct geographic distributions are recognized. Genetic differences among these populations might be a factor underlying geographic variation in gastric cancer incidence. Relatively little is known about the genomic features of African H. pylori strains compared to other populations of strains. In this study, we first analyzed the genomes of H. pylori strains from seven globally distributed populations or subpopulations and identified encoded proteins that exhibited the highest levels of sequence divergence. These included secreted proteins, an LPS glycosyltransferase, fucosyltransferases, proteins involved in molybdopterin biosynthesis, and Clp protease adaptor (ClpS). Among proteins encoded by the cag pathogenicity island, CagA and CagQ exhibited the highest levels of sequence diversity. We then identified proteins in strains of Western African origin (classified as hspWAfrica by MLST analysis) with sequences that were highly divergent compared to those in other populations of strains. These included ATP-dependent Clp protease, ClpS, and proteins of unknown function. Three of the divergent proteins sequences identified in West African strains were characterized by distinct insertions or deletions up to 8 amino acids in length. These polymorphisms in rapidly evolving proteins represent robust genetic signatures for H. pylori strains of West African origin.

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Genetic signatures for Helicobacter pylori strains of West African origin

November Genetic signatures for Helicobacter pylori strains of West African origin Kennady K. Bullock 0 1 2 Carrie L. Shaffer 0 2 Andrew W. Brooks 0 2 Ousman Secka 0 2 Mark H. Forsyth 0 2 Mark S. McClain 0 1 2 Timothy L. Cover 0 1 2 0 Institutes of Health AI118932, AI039657, CA116087 (TC); and U.S. Department of Veterans Affairs 2I01BX000627, TC 1 Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 2 Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, United States of America, 3 Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 4 Medical Research Council Unit The Gambia , Banjul , The Gambia , 5 Department of Biology, The College of William and Mary, Williamsburg, Virginia, United States of America, 6 Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 7 Veterans Affairs Tennessee Valley Healthcare System , Nashville, Tennessee , United States of America 2 Editor: Masaru Katoh, National Cancer Center , JAPAN Helicobacter pylori is a genetically diverse bacterial species that colonizes the stomach in about half of the human population. Most persons colonized by H. pylori remain asymptomatic, but the presence of this organism is a risk factor for gastric cancer. Multiple populations and subpopulations of H. pylori with distinct geographic distributions are recognized. Genetic differences among these populations might be a factor underlying geographic variation in gastric cancer incidence. Relatively little is known about the genomic features of African H. pylori strains compared to other populations of strains. In this study, we first analyzed the genomes of H. pylori strains from seven globally distributed populations or subpopulations and identified encoded proteins that exhibited the highest levels of sequence divergence. These included secreted proteins, an LPS glycosyltransferase, fucosyltransferases, proteins involved in molybdopterin biosynthesis, and Clp protease adaptor (ClpS). Among proteins encoded by the cag pathogenicity island, CagA and CagQ exhibited the highest levels of sequence diversity. We then identified proteins in strains of Western African origin (classified as hspWAfrica by MLST analysis) with sequences that were highly divergent compared to those in other populations of strains. These included ATP-dependent Clp protease, ClpS, and proteins of unknown function. Three of the divergent proteins sequences identified in West African strains were characterized by distinct insertions or deletions up to 8 amino acids in length. These polymorphisms in rapidly evolving proteins represent robust - Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Competing interests: The authors have declared that no competing interests exist. genetic signatures for H. pylori strains of West African origin. Introduction Helicobacter pylori is a Gram-negative bacterial species that persistently colonizes the stomach in about half of the world's human population. H. pylori has a high mutation rate, and strains from unrelated persons exhibit a high level of genetic diversity [1±4]. H. pylori strains from various geographic areas can be classified into distinct populations and subpopulations, based on multi-locus sequence typing (MLST) analysis [5±7]. H. pylori genetic diversity decreases with increasing geographic distance from Africa, the origin of Homo sapiens [ 6 ]. Therefore, H. pylori is thought to have co-evolved with humans over the past 100,000 years [8], and geo graphic differences among H. pylori strains reflect ancient human migration events [ 5, 6, 9 ]. Despite H. pylori’s long evolutionary history with humans, H. pylori colonization is a risk factor for the development of non-cardia gastric cancer and peptic ulcer disease. In 1994, the International Agency for Research on Cancer classified H. pylori as a bacterial carcinogen [10]. Genetic variation among H. pylori strains is known to be an important factor influencing the outcome of infection [ 1, 11 ]. For example, strains that contain the cag pathogenicity island (PAI), which encodes CagA (a secreted effector protein) and a type IV secretion system [12± 15], are associated with a higher risk of gastric cancer or peptic ulceration compared to strains that do not contain the cag PAI [ 1, 11 ]. Similarly, strains that produce active forms of the VacA toxin and strains that produce specific outer membrane proteins have been linked to an increased risk of gastric cancer or peptic ulceration [11, 16]. The prevalence of H. pylori infection and the incidence of gastric cancer each vary geo graphically [ 17, 18 ]. In general, developing countries have a higher prevalence of H. pylori infection than developed countries. East Asi (...truncated)


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Kennady K. Bullock, Carrie L. Shaffer, Andrew W. Brooks, Ousman Secka, Mark H. Forsyth, Mark S. McClain, Timothy L. Cover. Genetic signatures for Helicobacter pylori strains of West African origin, PLOS ONE, 2017, Volume 12, Issue 11, DOI: 10.1371/journal.pone.0188804