The overall goal of the exploratory R21 program studies proposed here is to better understand how the gastric pathogen Helicobacter pylori (Hp) evolves in human populations especially the impact of genetic drift and selection on genes important in bacterial-host interactions;and ultimately, the impact of a strain's evolutionary history on its vigor of infection, virulence and the risk of human disease. As background, Hp is implicated in peptic ulcer and gastric cancer, although most infections are benign, and some may even be beneficial. Hp is extremely diverse genetically: independent isolates typically differ by ~3% in DNA sequence of conserved housekeeping genes;and different sets of genotypes predominate in different regions (e.g., West Europe vs. East Asia). In preliminary studies we found strains from a remote Peruvian Amazon tribal community, the `Shima', to be unusually homogeneous in sequence at most loci, but highly divergent in two adhesin genes;in addition, representative genes from these Shimaa strains were Asian-like, whereas those from urban Peruvians (who are also of primarily Asian ancestry >12,000 yrs ago) seemed mostly European genetically. We hypothesize that Shimaa strain genetic uniformity reflects frequent inter-family transmission in this small closed community, and effective selection for best-adapted strains;and that adhesin gene diversity reflects selection for frequent change in host receptor affinities. Here we propose (i) to sequence the genomes of two or more representative Shimaa strains;(ii) to search these genomes for genes or allele types not represented in other already sequenced Hp genomes [each from ethnic Europeans];and (iii) to find other rapidly evolving genes by comparative hybridization using microarrays designed from Shimaa strain genome sequences. Comparative studies of strains from special populations such as these can be immensely productive, leading to special evolutionary insights, generally applicable to diverse pathogenic, commensal and beneficial microbial species.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Mills, Melody
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Pirini, Francesca; Noazin, Sassan; Jahuira-Arias, Martha H et al. (2017) Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies. Oncotarget 8:38501-38516
Kersulyte, Dangeruta; Bertoli, M Teresita; Tamma, Sravya et al. (2015) Complete Genome Sequences of Two Helicobacter pylori Strains from a Canadian Arctic Aboriginal Community. Genome Announc 3:
Secka, Ousman; Moodley, Yoshan; Antonio, Martin et al. (2014) Population genetic analyses of Helicobacter pylori isolates from Gambian adults and children. PLoS One 9:e109466
Scliar, Marilia O; Gouveia, Mateus H; Benazzo, Andrea et al. (2014) Bayesian inferences suggest that Amazon Yunga Natives diverged from Andeans less than 5000 ybp: implications for South American prehistory. BMC Evol Biol 14:174
Lind, Judith; Backert, Steffen; Pfleiderer, Klaus et al. (2014) Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of Western-type Helicobacter pylori strains. PLoS One 9:e96488
Tegtmeyer, Nicole; Rivas Traverso, Francisco; Rohde, Manfred et al. (2013) Electron microscopic, genetic and protein expression analyses of Helicobacter acinonychis strains from a Bengal tiger. PLoS One 8:e71220
Duncan, Stacy S; Bertoli, M Teresita; Kersulyte, Dangeruta et al. (2013) Genome Sequences of Three hpAfrica2 Strains of Helicobacter pylori. Genome Announc 1:
Secka, Ousman; Berg, Douglas E; Antonio, Martin et al. (2013) Antimicrobial susceptibility and resistance patterns among Helicobacter pylori strains from The Gambia, West Africa. Antimicrob Agents Chemother 57:1231-7
Kersulyte, Dangeruta; Rossi, Mirko; Berg, Douglas E (2013) Sequence divergence and conservation in genomes of Helicobacter cetorum strains from a dolphin and a whale. PLoS One 8:e83177
Debowski, Aleksandra W; Carnoy, Christophe; Verbrugghe, Phebe et al. (2012) Xer recombinase and genome integrity in Helicobacter pylori, a pathogen without topoisomerase IV. PLoS One 7:e33310

Showing the most recent 10 out of 15 publications