title: Natural variation in populations of persistently colonizing bacteria affect human host cell phenotype.
abstract: The highly diverse bacterium Helicobacter pylori, which persistently colonizes the human stomach, provides models to study the role of genome plasticity in host adaptation. Within H. pylori populations from 2 colonized individuals, intragenomic recombination between cagA DNA repeat sequences leads to deletion or duplication of tyrosine phosphorylation sites in the CagA protein, which is injected by a type IV secretion system into host cells. Experimental coculture of gastric epithelial cells with the strains containing these naturally occurring CagA phosphorylation site variants induced markedly divergent host cell morphologic responses. Mutants were constructed in which a phosphorylation site was either added or deleted in the expressed CagA protein; coculture studies confirmed that the naturally occurring differences in CagA phosphorylation are responsible for the observed phenotypic variation. These findings indicate that within an individual host, intragenomic recombination between H. pylori repetitive DNA produces strain variants differing in their signals to host cells.
authors.affiliation: Departments of Medicine and Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: Rahul A
authors.initials: RA
authors.lastname: Aras
authors.forename: Yongchan
authors.initials: Y
authors.lastname: Lee
authors.forename: Sung-Kook
authors.initials: SK
authors.lastname: Kim
authors.forename: Dawn
authors.initials: D
authors.lastname: Israel
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Blaser
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D048429:Cell Size; D018920:Coculture Techniques; D005753:Gastric Mucosa / Q000166:cytology* / Q000382:microbiology*; D014644:Genetic Variation; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010641:Phenotype; D010766:Phosphorylation; D011995:Recombination, Genetic / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D013270:Stomach / Q000166:cytology / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori