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Open Access Research article

Phylogeographic evidence of cognate recognition site patterns and transformation efficiency differences in H. pylori: theory of strain dominance

Ana Maldonado-Contreras12, Shrinivasrao P Mane3, Xue-Song Zhang4, Luis Pericchi5, Teresa Alarcón6, Monica Contreras7, Bodo Linz8, Martin J Blaser49 and María Gloria Domínguez-Bello14*

Author Affiliations

1 Department of Biology, University of Puerto Rico, Río Piedras, San Juan, PR, USA

2 Microbiology and Physiological Systems Department, University of Massachusetts Medical School, Worcester, MA, USA

3 Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA, USA

4 Department of Medicine, New York University Langone Medical Center, Manhattan, NY, USA

5 Department of Mathematic, University of Puerto Rico, Río Piedras, San Juan, USA

6 Servicio de Microbiología, Hospital Universitario de la Princesa, Madrid, Spain

7 Venezuelan Institute of Scientific Research (IVIC), San Antonio de los Altos, Venezuela

8 Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA

9 New York Harbor Veterans Affairs Medical Center, Manhattan, NY, USA

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BMC Microbiology 2013, 13:211  doi:10.1186/1471-2180-13-211

Published: 19 September 2013



Helicobacter pylori has diverged in parallel to its human host, leading to distinct phylogeographic populations. Recent evidence suggests that in the current human mixing in Latin America, European H. pylori (hpEurope) are increasingly dominant at the expense of Amerindian haplotypes (hspAmerind). This phenomenon might occur via DNA recombination, modulated by restriction-modification systems (RMS), in which differences in cognate recognition sites (CRS) and in active methylases will determine direction and frequency of gene flow. We hypothesized that genomes from hspAmerind strains that evolved from a small founder population have lost CRS for RMS and active methylases, promoting hpEurope’s DNA invasion. We determined the observed and expected frequencies of CRS for RMS in DNA from 7 H. pylori whole genomes and 110 multilocus sequences. We also measured the number of active methylases by resistance to in vitro digestion by 16 restriction enzymes of genomic DNA from 9 hpEurope and 9 hspAmerind strains, and determined the direction of DNA uptake in co-culture experiments of hspAmerind and hpEurope strains.


Most of the CRS were underrepresented with consistency between whole genomes and multilocus sequences. Although neither the frequency of CRS nor the number of active methylases differ among the bacterial populations (average 8.6 ± 2.6), hspAmerind strains had a restriction profile distinct from that in hpEurope strains, with 15 recognition sites accounting for the differences. Amerindians strains also exhibited higher transformation rates than European strains, and were more susceptible to be subverted by larger DNA hpEurope-fragments than vice versa.


The geographical variation in the pattern of CRS provides evidence for ancestral differences in RMS representation and function, and the transformation findings support the hypothesis of Europeanization of the Amerindian strains in Latin America via DNA recombination.

H. pylori; Haplotypes; Restriction-Modification system; Recombination