Helicobacter pylori (Hp) are one of the most genetically diverse of bacterial species. Our preliminary DNA-based phylogenetic analyses showed that genotypes of Hp in Spain differ from those in East Asia, and that genotypes of Hp from Peruvians in Lima are mostly Spanish-like. The studies proposed for this grant period have four main specific aims.
AIM 1. To better understand Hp genetic diversity and genome evolution. We will extend current phylogenetic studies to Hp strains from other Amerind people in Latin America, to test predictions that most such Hp strains will also be Spanish-like at most loci. Any Hp population found to be rich in alleles unlike those of Spain will be examined further. Hp from elsewhere in Europe, Asia and Africa will also be studied (i) to better understand Hp population genetic structure worldwide, (ii) test predictions that Hp gene pools in Japan and Spain represent subsets of more genetically diverse East Asian and European gene pools, respectively.
AIM 2. To identify naturally occurring allele differences that affect fitness and understand their basis. We will test the generality of our finding that East Asian-type alleles of the comB9 gene are abundant in Hp from Amerinds in Lima, and test if this reflects selection. More generally, additional cases of unusual abundance of particular alleles or genes will be investigated to identify bacterial traits important in specificity of host interaction. Effects on fitness of candidate genes or alleles will be examined using genetically manipulated rodent-adapted Hp strains and mouse and gerbil infection models.
AIM 3. To examine Hp evolutionary dynamics within family units, Hp strains from parents and children in individual Peruvian families will be genotyped to gain insights into relatedness, intrafamilial vs. community transmission, and mutation, recombination, and selection on Hp in societies where overall risks of infection are high.
AIM 4. To detect transmission between communities, mixed infection, and potential for recombination. Hp from Japanese Peruvians will be genotyped to detect (i) retention of ancestral Japanese-type genes, vs. community acquisition of putative Native Peruvian (Spanish-type) strains; (ii) mixed infections, especially involving strains of different ethnic origins, (iii) extent of recombination in a brief time frame, and (iv) selection for particular genes or alleles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK063041-05
Application #
7247265
Study Section
Genetics Study Section (GEN)
Program Officer
Karp, Robert W
Project Start
2003-06-01
Project End
2009-05-31
Budget Start
2007-06-01
Budget End
2009-05-31
Support Year
5
Fiscal Year
2007
Total Cost
$293,681
Indirect Cost
Name
Washington University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Bugaytsova, Jeanna A; Björnham, Oscar; Chernov, Yevgen A et al. (2017) Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. Cell Host Microbe 21:376-389
Kupcinskas, Limas; Rasmussen, Lone; Jonaitis, Laimas et al. (2013) Evolution of Helicobacter pylori susceptibility to antibiotics during a 10-year period in Lithuania. APMIS 121:431-6
Suzuki, Masato; Kiga, Kotaro; Kersulyte, Dangeruta et al. (2011) Attenuated CagA oncoprotein in Helicobacter pylori from Amerindians in Peruvian Amazon. J Biol Chem 286:29964-72
Choi, Sung Sook; Chivers, Peter T; Berg, Douglas E (2011) Point mutations in Helicobacter pylori's fur regulatory gene that alter resistance to metronidazole, a prodrug activated by chemical reduction. PLoS One 6:e18236
Kersulyte, Dangeruta; Kalia, Awdhesh; Gilman, Robert H et al. (2010) Helicobacter pylori from Peruvian amerindians: traces of human migrations in strains from remote Amazon, and genome sequence of an Amerind strain. PLoS One 5:e15076
Styer, Cathy M; Hansen, Lori M; Cooke, Cara L et al. (2010) Expression of the BabA adhesin during experimental infection with Helicobacter pylori. Infect Immun 78:1593-600
Kersulyte, Dangeruta; Lee, Wookon; Subramaniam, Dharmalingam et al. (2009) Helicobacter Pylori's plasticity zones are novel transposable elements. PLoS One 4:e6859
Suzuki, Masato; Mimuro, Hitomi; Kiga, Kotaro et al. (2009) Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation. Cell Host Microbe 5:23-34
Gehmert, Sebastian; Velapatino, Billie; Herrera, Phabiola et al. (2009) Interleukin-1 beta single-nucleotide polymorphism's C allele is associated with elevated risk of gastric cancer in Helicobacter pylori-infected Peruvians. Am J Trop Med Hyg 81:804-10
Galvez-Buccollini, Juan A; DeLea, Suzanne; Herrera, Phabiola M et al. (2009) Sexual behavior and drug consumption among young adults in a shantytown in Lima, Peru. BMC Public Health 9:23

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