article · Nature
A distinct ecospecies of Helicobacter pylori, designated Hardy, has been identified alongside the common Ubiquitous form. While sharing ancestry across most of the genome with regional Ubiquitous strains, Hardy bacteria display nearly fixed single-nucleotide differences across one hundred genes. Many of these genes encode outer membrane proteins and host interaction factors. Most Hardy strains possess two extra copies of the vacuolating cytotoxin VacA and an alternative, iron-dependent urease rather than the standard nickel-dependent enzyme. Currently found in Indigenous communities in Siberia and the Americas, as well as in mammalian lineages following host jumps, these two bacterial lineages coexisted in human stomachs prior to prehistoric migrations out of Africa. This demonstrates that bacterial populations can develop and maintain sharply divergent ecological and adaptive strategies over long evolutionary timescales, even while undergoing continuous genetic exchange between coexisting strains.
Understanding the diversity of Helicobacter pylori is important because the bacterium causes stomach ulcers and gastric cancer. Revealing that two distinct forms have coexisted since before modern human migration from Africa sheds light on bacterial evolution, host adaptation, and the long-term persistence of distinct virulence factors across different human populations and animal hosts.
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Helicobacter pylori disturbs the stomach lining during long-term colonization of its human host, with sequelae including ulcers and gastric cancer<sup>1,2</sup>. Numerous H. pylori virulence factors have been identified, showing extensive geographic variation<sup>1</sup>. Here we identify a 'Hardy' ecospecies of H. pylori that shares the ancestry of 'Ubiquitous' H. pylori from the same region in most of the genome but has nearly fixed single-nucleotide polymorphism differences in 100 genes, many of which encode outer membrane proteins and host interaction factors. Most Hardy strains have a second urease, which uses iron as a cofactor rather than nickel<sup>3</sup>, and two additional copies of the vacuolating cytotoxin VacA. Hardy strains currently have a limited distribution, including in Indigenous populations in Siberia and the Americas and in lineages that have jumped from humans to other mammals. Analysis of polymorphism data implies that Hardy and Ubiquitous coexisted in the stomachs of modern humans since before we left Africa and that both were dispersed around the world by our migrations. Our results also show that highly distinct adaptive strategies can arise and be maintained stably within bacterial populations, even in the presence of continuous genetic exchange between strains.
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DOI: 10.1038/s41586-024-07991-z
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