Coadaptation of Helicobacter pylori and humans: ancient history, modern implications
John C. Atherton, Martin J. Blaser
John C. Atherton, Martin J. Blaser
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Coadaptation of Helicobacter pylori and humans: ancient history, modern implications

Abstract

Humans have been colonized by Helicobacter pylori for at least 50,000 years and probably throughout their evolution. H. pylori has adapted to humans, colonizing children and persisting throughout life. Most strains possess factors that subtly modulate the host environment, increasing the risk of peptic ulceration, gastric adenocarcinoma, and possibly other diseases. H. pylori genes encoding these and other factors rapidly evolve through mutation and recombination, changing the bacteria-host interaction. Although immune and physiologic responses to H. pylori also contribute to pathogenesis, humans have evolved in concert with the bacterium, and its recent absence throughout the life of many individuals has led to new human physiological changes. These may have contributed to recent increases in esophageal adenocarcinoma and, more speculatively, other modern diseases.

Authors

John C. Atherton, Martin J. Blaser

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Figure 3

Mechanisms for generating genetic diversity in H. pylori.

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Mechanisms for generating genetic diversity in H. pylori. (A) Slippe...
(A) Slipped-strand mispairing in a homopolymeric tract, leading to phase variation in surface antigen expression. Lewis (LeX and LeY) expression in single colonies of an H. pylori strain were determined by ELISA, with transformed converted mean OD units (TCMO) calculated. Two major population groupings were observed, based on frame-status of futC, the gene encoding α-1,2-fucosytransferase. Reproduced with permission from Microbes and infection (S28). (B–D) Polymorphisms in the gene mutY, which encodes DNA glycosylase MutY. (B). Genotypes of 413 mutY homonucleotide tracts from the H. pylori multilocus sequence typing (MLST) database. (C) Chromatograph of the mutY homonucleotide with seven adenines (out of frame). (D) Chromatograph of in-frame mutY (eight adenines). When mutY is out of frame, the H. pylori cells have a mutator phenotype, augmenting genomic point mutation. Reproduced with permission from Journal of bacteriology (S29). (E–G) Effect of exposure to RNS and ROS in frequency of deletions involving DNA repeats. (E) Deletion cassette. Cells with this were exposed to RNS (F) or ROS (G) and deletion frequency was calculated. Asterisks indicate significant (P < 0.05) increases in point mutation frequencies when compared with those calculated for cells incubated in 0 nM of SNP or methyl viologen. aphA, gene encoding aminoglycoside resistance; CAT, chloramphenicol acetyl transferase; CmR, resistant to chloramphenicol; IDS, identical repeat sequence; KanS, susceptible to kanamycin. Reproduced with permission from FASEB journal (S27). (H) Proposed mechanism of RuvB/RecG Holliday junction resolution. Two H. pylori DNA processing pathways may compete for the same Holliday junction intermediate, which can branch migrate (left pathway) because of RuvAB and be resolved by RuvC, restoring replication fork, enabling loading of the replisome (small oval). Alternatively, (middle pathway) RecG (gray circle) can branch migrate Holliday junctions, but without resolution, leading to cell death. Addition of RusA restores the RecG pathway, leading to recombinational repair. The incomplete recG pathway reflects a tension between DNA repair and antirepair. Reproduced with permission from Journal of bacteriology (S26).