title: Slow genetic divergence of Helicobacter pylori strains during long-term colonization.
abstract: The genetic variability of Helicobacter pylori is known to be high compared to that of many other bacterial species. H. pylori is adapted to the human stomach, where it persists for decades, and adaptation to each host results in every individual harboring a distinctive bacterial population. Although clonal variants may exist within such a population, all isolates are generally genetically related and thus derived from a common ancestor. We sought to determine the rate of genetic change of H. pylori over 9 years in two asymptomatic adult patients. Arbitrary primed PCR confirmed the relatedness of individual subclones within a patient. Furthermore, sequencing of 10 loci ( approximately 6,000 bp) in three subclones per time and patient revealed only two base pair changes among the subclones from patient I. All sequences were identical among the patient II subclones. However, PCR amplification of the highly divergent gene amiA revealed great variation in the size of the gene between the subclones within each patient. Thus, both patients harbored a single strain with clonal variants at both times. We also studied genetic changes in culture- and mouse-passaged strains, and under both conditions no genetic divergence was found. These results suggest that previous estimates of the rate of genetic change in H. pylori within an individual might be overestimates.
authors.affiliation: Department of Bacteriology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Lundin
authors.forename: Britta
authors.initials: B
authors.lastname: Björkholm
authors.forename: Ilya
authors.initials: I
authors.lastname: Kupershmidt
authors.forename: Magnus
authors.initials: M
authors.lastname: Unemo
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Dan I
authors.initials: DI
authors.lastname: Andersson
authors.forename: Lars
authors.initials: L
authors.lastname: Engstrand
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D005075:Biological Evolution; D002352:Carrier Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005753:Gastric Mucosa / Q000382:microbiology; D014644:Genetic Variation; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008074:Lipoproteins / Q000235:genetics; D008795:Metronidazole / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008074:Lipoproteins; D008795:Metronidazole