Abstract

BackgroundHelicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H. pylori is one of the most genetically variable human pathogens and the ability of the bacterium to bind to the host epithelium as well as the presence of different virulence factors and genetic variants within these genes have been associated with disease severity. Nicaragua has particularly high gastric cancer incidence and we therefore studied Nicaraguan clinical H. pylori isolates for factors that could contribute to cancer risk.MethodsThe complete genomes of fifty-two Nicaraguan H. pylori isolates were sequenced and assembled de novo, and phylogenetic and virulence factor analyses were performed.ResultsThe Nicaraguan isolates showed phylogenetic relationship with West African isolates in whole-genome sequence comparisons and with Western and urban South- and Central American isolates using MLSA (Multi-locus sequence analysis). A majority, 77 % of the isolates carried the cancer-associated virulence gene cagA and also the s1/i1/m1 vacuolating cytotoxin, vacA allele combination, which is linked to increased severity of disease. Specifically, we also found that Nicaraguan isolates have a blood group-binding adhesin (BabA) variant highly similar to previously reported BabA sequences from Latin America, including from isolates belonging to other phylogenetic groups. These BabA sequences were found to be under positive selection at several amino acid positions that differed from the global collection of isolates.ConclusionThe discovery of a Latin American BabA variant, independent of overall phylogenetic background, suggests hitherto unknown host or environmental factors within the Latin American population giving H. pylori isolates carrying this adhesin variant a selective advantage, which could affect pathogenesis and risk for sequelae through specific adherence properties.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0619-y) contains supplementary material, which is available to authorized users.

Highlights

  • Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer

  • The virulence factors cagA, vacuolating cytotoxin (vacA), babA and sabA were analysed in more detail and we found that a majority of the isolates carried cagA, that the vacA s1/i1/m1 genotype co-occurred with cagA presence in almost all cases, and that CagA was of western type

  • Multi-locus sequence analysis place Nicaraguan isolates closer to urban South American and European isolates To compare the Nicaraguan isolates in a larger context an MLSA phylogenetic tree was constructed using the 44 complete genomes used for SNP phylogeny, all Nicaraguan draft genomes, and available draft genomes deposited in GenBank at the time of analysis

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Summary

Introduction

Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H. pylori infection is able to cause severe clinical outcomes such as duodenal and gastric ulcers, and is classified as a carcinogen causing gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. The incidence rates of these diseases vary world-wide with e.g., considerably higher incidence of gastric cancer in East Asia, Central America and South America [2] What leads to this divergence in clinical outcome is not entirely known, but both host genetics modulating the immune response towards the infection, as well as bacterial genetics and environmental factors such as smoking and high intake of salt has been shown to play a role [3]

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