Expansion of European vacA and cagA alleles to East-Asian Helicobacter pylori strains in Cambodia Sebastien Breurec a,b,⇑ , Bertrand Guillard b , Sopheak Hem b , Konstantinos S. Papadakos c , Sylvain Brisse d , Michel Huerre e , Didier Monchy b,f , Chakravuth Oung g , Dionyssios N. Sgouras c , Tek Sreng Tan h , Jean-Michel Thiberge d , Sirenda Vong i , Josette Raymond j , Bodo Linz k a Unité de Bactériologie Médicale et Environnementale, Institut Pasteur, 36 Avenue Pasteur, BP 220, Dakar, Senegal b Unité de Biologie Médicale, Institut Pasteur, 5 Boulevard Monivong, BP 983, Phnom Penh, Cambodia c Laboratory of Medical Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, Athens 11521, Greece d Plate-forme Génotypage des Pathogènes et Santé Publique, Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris Cedex 15, France e Unité de Recherche et d’Expertises en Histotechnologie et Pathologie, Institut Pasteur, Paris, 25-28 rue du Docteur Roux, 75724 Paris Cedex 15, France f Laboratoire de Biologie médicale, Institut Pasteur, BP923, Bangui, République Centrafricaine, France g Gastroenterology and Liver Unit, Calmette Hospital, 3 boulevard Monivong, Phnom Penh, Cambodia h Private Medical Center, No. 29 street 288, Boeng Kengkang 1, Chamkamon, Phnom Penh, Cambodia i Unité d’Epidémiologie et de Santé Publique, Institut Pasteur, 5 Boulevard Monivong, BP 983, Cambodia j Unité Postulante Pathogenèse de Helicobacter, Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris Cedex 15, France k Department of Biochemistry and Molecular Biology, The Pennsylvania State University, 312 Wartik Lab, University Park, PA 16802, USA article info Article history: Received 4 May 2011 Received in revised form 4 August 2011 Accepted 7 August 2011 Available online 17 August 2011 Keywords: H. pylori cagA vacA Recombination Genetic population Cambodia abstract Helicobacter pylori infection is associated with gastric cancer (GC). The highest incidence rates have been described in Asia, but regional variations exist that do not match the distribution of infection prevalence rates. The aim of the study was to examine the possible contribution of H. pylori virulence factors to geo- graphic differences in the incidence of GC across East and Southeast Asia. We studied 66 isolates from Cambodian patients that had previously been assigned to two genetic populations based on sequences of seven housekeeping genes, namely hpEurope (n = 34, 51.5%) and hpEastAsia, subpopulation hspEAsia (n = 32, 48.5%). These strains were characterized with respect to vacA polymorphism and cagA status by PCR, and the CagA C-terminal region was sequenced. We also sequenced the complete cagA gene from 10 hpEurope and 10 hspEAsia strains chosen at random. The cagA gene was present in 92.4% of the 66 iso- lates and was mainly of Western type (n = 36, 59.0%). hspEAsia strains carrying East-Asian CagA and the m1-type vacA allele (15.2%) were less frequent among the 66 Cambodian isolates than reported in East Asian countries, a finding that might partly explain the intermediate incidence of GC in Cambodia, and by extension, in Southeast Asia (except for Vietnam). The observed high prevalence of s1a alleles (34.4%) and Western CagA (28.1%) among hspEAsia strains indicates frequent introgression of European vacA and cagA alleles into East Asian H. pylori strains. This expansion might have severe consequences for individual disease outcome. Ó 2011 Elsevier B.V. All rights reserved. 1. Introduction Helicobacter pylori infects the gastric mucosa of more than half the world population. Although all infected individuals develop H. pylori-associated gastritis, only a small percentage of colonized individuals develop severe gastroduodenal diseases such as gastric and duodenal ulcer (10%), or gastric adenocarcinoma and MALT lymphoma (1–4%) (Hatakeyama, 2009). Outcome of the infection is dependent on host, environmental and H. pylori virulence factors. H. pylori isolates have been subdivided into distinct (sub-) pop- ulations on the basis of sequence differences in seven core genes, with specific geographic distributions that reflect ancient human migrations (Falush et al., 2003b; Linz et al., 2007; Moodley et al., 2009; Tay et al., 2009): hpEurope (present in Europe, the Middle East, India and Iran), hpNEAfrica (present in Northeast Africa), hpAfrica1 (present in Western Africa and South Africa), hpAfrica2 1567-1348/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.meegid.2011.08.007 Abbreviations: cag PAI, cag pathogenicity island; EPIYA, Glu-Pro-Ile-Tyr-Ala; GC, Gastric carcinoma; SH2, cytoplasmic Src homology 2; SHP-2, Src homology 2 phosphatase; NFAT, nuclear factor of activated T cells. ⇑ Corresponding author at: Unité de Bactériologie Médicale et Environnementale, Institut Pasteur, 36 Avenue Pasteur, BP 220, Dakar, Senegal. Tel.: +221 33 839 92 30; fax: +221 33 822 70 52. E-mail address: sbreurec@pasteur.sn (S. Breurec). Infection, Genetics and Evolution 11 (2011) 1899–1905 Contents lists available at SciVerse ScienceDirect Infection, Genetics and Evolution journal homepage: www.elsevier.com/locate/meegid