RESUMO
BACKGROUND: The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes. PRINCIPAL FINDINGS: Housekeeping gene sequences from H. pylori from residents of an Amerindian village in the Peruvian Amazon, Shimaa, were related to, but not intermingled with, those from Asia. This suggests descent of Shimaa strains from H. pylori that had infected the people who migrated from Asia into The Americas some 15,000+ years ago. In contrast, European type sequences predominated in strains from Amerindian Lima shantytown residents, but with some 12% Amerindian or East Asian-like admixture, which indicates displacement of ancestral purely Amerindian strains by those of hybrid or European ancestry. The genome of one Shimaa village strain, Shi470, was sequenced completely. Its SNP pattern was more Asian- than European-like genome-wide, indicating a purely Amerind ancestry. Among its unusual features were two cagA virulence genes, each distinct from those known from elsewhere; and a novel allele of gene hp0519, whose encoded protein is postulated to interact with host tissue. More generally, however, the Shi470 genome is similar in gene content and organization to those of strains from industrialized countries. CONCLUSIONS: Our data indicate that Shimaa village H. pylori descend from Asian strains brought to The Americas many millennia ago; and that Amerind strains are less fit than, and were substantially displaced by, hybrid or European strains in less isolated communities. Genome comparisons of H. pylori from Amerindian and other communities should help elucidate evolutionary forces that have shaped pathogen populations in The Americas and worldwide.
Assuntos
Genoma Bacteriano/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Indígenas Sul-Americanos , América , Sequência de Aminoácidos , Ásia , Proteínas de Bactérias/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Emigração e Imigração , Europa (Continente) , Variação Genética , Helicobacter pylori/classificação , Helicobacter pylori/isolamento & purificação , Humanos , Dados de Sequência Molecular , Peru , Filogenia , Dinâmica Populacional , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Fatores de TempoRESUMO
The efficiency of transmission of a pathogen within families compared with that between unrelated persons can affect both the strategies needed to control or eradicate infection and how the pathogen evolves. In industrialized countries, most cases of transmission of the gastric pathogen Helicobacter pylori seems to be from mother to child. An alternative model, potentially applicable among the very poor in developing countries, where infection is more common and the sanitary infrastructure is often deficient, invokes frequent transmission among unrelated persons, often via environmental sources. In the present study, we compared the genotypes of H. pylori from members of shantytown households in Peru to better understand the transmission of H. pylori in developing-country settings. H. pylori cultures and/or DNAs were obtained with informed consent by the string test (a minimally invasive alternative to endoscopy) from at least one child and one parent from each of 62 families. The random amplified polymorphic DNA fingerprints of 57 of 81 (70%) child-mother strain pairs did not match, nor did the diagnostic gene sequences (>1% DNA sequence difference), independent of the child's age (range, 1 to 39 years). Most strains from siblings or other paired family members were also unrelated. These results suggest that H. pylori infections are often community acquired in the society studied. Transmission between unrelated persons should facilitate the formation of novel recombinant genotypes by interstrain DNA transfer and selection for genotypes that are well suited for individual hosts. It also implies that the effective prevention of H. pylori infection and associated gastroduodenal disease will require anti-H. pylori measures to be applied communitywide.
Assuntos
Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Adolescente , Adulto , Técnicas de Tipagem Bacteriana , Criança , Pré-Escolar , Impressões Digitais de DNA , DNA Bacteriano/genética , Países em Desenvolvimento , Saúde da Família , Feminino , Genótipo , Infecções por Helicobacter/transmissão , Helicobacter pylori/isolamento & purificação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Peru/epidemiologia , Técnica de Amplificação ao Acaso de DNA Polimórfico , Análise de Sequência de DNARESUMO
We compared the robustness and discriminatory power of the enterobacterial repetitive intergenic consensus (ERIC) and random amplified polymorphic DNA (RAPD) fingerprinting methods for detecting cases of mixed Helicobacter pylori infection in Peruvian shantytown residents. H. pylori isolates from 63 participants were cultured, and five single colonies and a pool of additional colonies from each participant were analyzed by ERIC-PCR and by RAPD tests with four 10-nucleotide primers (one primer per reaction). There was 94% agreement between the ERIC and RAPD profiles in classifying sets of isolates as uniform versus closely related but not identical versus probably unrelated, indicating a high kappa statistic of 0.8942. Subtle differences in related ERIC or RAPD patterns likely reflect gene transfer between strains, recombination, and/or mutation, whereas markedly different patterns reflect infection by unrelated strains. At least half of infected shantytown residents seemed to carry more than one H. pylori strain, although in 19 of 31 persons, the strains were closely related. Three RAPD tests, each with a different primer, were needed to achieve the sensitivity of one ERIC test. ERIC-PCR constitutes a resource- and time-efficient method for H. pylori strain differentiation.