Helicobacter pylori (Hp), one of the most genetically diverse of bacterial species, chronically infects the gastric mucosa of more than half of all persons world wide. It is the major cause of severe gastritis and peptic ulcers, and a risk factor for gastric cancer, although most infections are asymptomatic. Infection is more common in Alaska Natives than in mainstream US populations, and the spectrum of associated diseases is distinct. Most striking is an Hp-associated hemorrhagic gastritis and iron deficiency anemia that is common only in Alaska Natives. Here the investigators propose to study the genetics of Hp from Alaska natives. First, they will seek to define the population genetic structure of Hp in Alaska Natives. In these experiments they will (a) test the view that the Alaska Native Hp gene pool is far less diverse than that in other human populations, (b) learn whether Hp from some regions or linguistic/ethnic groups of Alaska Natives differs significantly from that in others, and (c) test the idea that Hp lineages in this population are far more nearly clonal (less scrambled by recombination) than has been seen in other human populations. They propose that recombination is important, assuming that Hp colonization of individual hosts is often associated with considerable adaptation on the part of the bacterium to that given person, and that the formation of recombinants during even transiently mixed infection can markedly speed this process. These tests will entail arbitrarily primed PCR (RAPD) typing of several hundred Hp isolates from Alaska Natives, and then multilocus DNA sequence typing (MLST) of informative gene loci from many representative strains. The data will also help assess whether much or any significant portion of the Hp gene pool of Alaska Natives is of Asian origin, as defined by studies of Hp isolates from Eastern China and Japan, and as might be expected if the ancestors of current Alaska Natives carried Hp with them when they migrated from Asia many millennia ago. Second, they will search for previously unknown genes affecting Hp virulence, with special interest in genes affecting the risk of hemorrhagic gastritis or iron deficiency anemia. This will be based on new subtractive hybridization and DNA microarray-based comparative genomic methods. Third, they will search for genes or alleles of divergent gene families that may contribute to the growth of individual strains in particular human hosts. This will entail analyses of recombinant derivatives of individual strains that emerge in Alaska Native populations, often, they postulate, as the result of selection for a gene or allele that may have been transferred from an unrelated Hp strain.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Hamilton, Frank A
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Washington University
Schools of Medicine
Saint Louis
United States
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Miernyk, Karen M; Bruden, Dana L; Bruce, Michael G et al. (2007) Dynamics of Helicobacter pylori-specific immunoglobulin G for 2 years after successful eradication of Helicobacter pylori infection in an American Indian and Alaska Native population. Clin Vaccine Immunol 14:85-6
Bruce, Michael G; Bruden, Dana L; McMahon, Brian J et al. (2006) Alaska sentinel surveillance for antimicrobial resistance in Helicobacter pylori isolates from Alaska native persons, 1999-2003. Helicobacter 11:581-8
Morris, Julie M; Reasonover, Alisa L; Bruce, Michael G et al. (2005) Evaluation of seaFAST, a rapid fluorescent in situ hybridization test, for detection of Helicobacter pylori and resistance to clarithromycin in paraffin-embedded biopsy sections. J Clin Microbiol 43:3494-6
Datta, S; Chattopadhyay, S; Patra, R et al. (2005) Most Helicobacter pylori strains of Kolkata in India are resistant to metronidazole but susceptible to other drugs commonly used for eradication and ulcer therapy. Aliment Pharmacol Ther 22:51-7
Suto, Hiroyuki; Zhang, Maojun; Berg, Douglas E (2005) Age-dependent changes in susceptibility of suckling mice to individual strains of Helicobacter pylori. Infect Immun 73:1232-4
Datta, Simanti; Chattopadhyay, Santanu; Chowdhury, Abhijit et al. (2005) Diagnosis and genotyping of Helicobacter pylori by polymerase chain reaction of bacterial DNA from gastric juice. J Gastroenterol Hepatol 20:1253-9
Kalia, Awdhesh; Mukhopadhyay, Asish K; Dailide, Giedrius et al. (2004) Evolutionary dynamics of insertion sequences in Helicobacter pylori. J Bacteriol 186:7508-20
McNulty, Shannon L; Mole, Beth M; Dailidiene, Daiva et al. (2004) Novel 180- and 480-base-pair insertions in African and African-American strains of Helicobacter pylori. J Clin Microbiol 42:5658-63
Chattopadhyay, Santanu; Patra, Rajashree; Ramamurthy, T et al. (2004) Multiplex PCR assay for rapid detection and genotyping of Helicobacter pylori directly from biopsy specimens. J Clin Microbiol 42:2821-4
Dailidiene, Daiva; Dailide, Giedrius; Ogura, Keiji et al. (2004) Helicobacter acinonychis: genetic and rodent infection studies of a Helicobacter pylori-like gastric pathogen of cheetahs and other big cats. J Bacteriol 186:356-65

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