Heterogeneity of Helicobacter pylori

Although many physicians view Helicobacter pylori strains as a homogenous group of organisms, it has become increasingly clear that populations in humans are highly diverse. This heterogeneity can be analyzed at two different levels: genotypic variation among strains and variations in H. pylori populations within an individual host. Genotypic variation includes point mutations in conserved genes (e.g. ureC), variation in the gene order on physical maps, mosaicism in conserved genes (e.g. vacAs1a), non-conserved genes (e.g. cagA) and extragenetic elements (e.g. IS605). Population differences include the observations that humans can be simultaneously infected with two or more H. pylori strains and that a single strain may represent a cluster of closely related organisms (a 'quasispecies'). The presence of multiple organisms within a host may occur as a result of recombination events leading to genetic shift, whereas ongoing mutation within a strain can lead to the formation of quasispecies by genetic drift. Over recent years it has become increasingly clear that observations on the fundamental biology of H. pylori have considerable clinical relevance. Several genotypic markers (e.g. cagA, vacA, sIa and iceA1) are associated with an increased risk of disease. Also, the multiplicity of infection and quasispecies indicates that analysis of a single H. pylori isolate is inaccurate for defining the genotype of H. pylori strains present in a patient. Global assays, such as serology, are more suitable. The aim of this paper is to review the general phenomenon of diversity in H. pylori and to describe particular heterogeneities that are related to clinical outcome.