title: Analysis of a single Helicobacter pylori strain over a 10-year period in a primate model.
abstract: Helicobacter pylori from different individuals exhibits substantial genetic diversity. However, the kinetics of bacterial diversification after infection with a single strain is poorly understood. We investigated evolution of H. pylori following long-term infection in the primate stomach; Rhesus macaques were infected with H. pylori strain USU101 and then followed for 10 years. H. pylori was regularly cultured from biopsies, and single colony isolates were analyzed. At 1-year, DNA fingerprinting showed that all output isolates were identical to the input strain; however, at 5-years, different H. pylori fingerprints were observed. Microarray-based comparative genomic hybridization revealed that long term persistence of USU101 in the macaque stomach was associated with specific whole gene changes. Further detailed investigation showed that levels of the BabA protein were dramatically reduced within weeks of infection. The molecular mechanisms behind this reduction were shown to include phase variation and gene loss via intragenomic rearrangement, suggesting strong selective pressure against BabA expression in the macaque model. Notably, although there is apparently strong selective pressure against babA, babA is required for establishment of infection in this model as a strain in which babA was deleted was unable to colonize experimentally infected macaques.
authors: Department of Medicine and United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Hui
authors: H
authors: Liu
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Jutta B
authors: JB
authors: Fero
authors: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors: Melissa
authors: M
authors: Mendez
authors: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Beth M
authors: BM
authors: Carpenter
authors: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Stephanie L
authors: SL
authors: Servetas
authors: Department of Medicine and United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Arifur
authors: A
authors: Rahman
authors: Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors: Matthew D
authors: MD
authors: Goldman
authors: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors: Thomas
authors: T
authors: Boren
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Nina R
authors: NR
authors: Salama
authors: Department of Medicine and United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address: douglas.merrell@usuhs.edu.
authors: D Scott
authors: DS
authors: Merrell
authors: Department of Medicine and United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Andre
authors: A
authors: Dubois
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D000818:Animals; D001706:Biopsy; D055028:Comparative Genomic Hybridization; D016172:DNA Fingerprinting; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D015321:Gene Rearrangement; D014644:Genetic Variation; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification*; D008137:Longitudinal Studies; D008253:Macaca mulatta; D046228:Microarray Analysis; D012641:Selection, Genetic; D013270:Stomach / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; C400429:BabA protein, Helicobacter pylori; D004269:DNA, Bacterial
keywords: Colonization; Evolution; Helicobacter pylori; Outer membrane protein; babA