Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2001 Dec 4;98(25):14625-30.
doi: 10.1073/pnas.251551698. Epub 2001 Nov 27.

Helicobacter pylori genetic diversity within the gastric niche of a single human host

D A Israel  1 , N Salama, U Krishna, U M Rieger, J C Atherton, S Falkow, R M Peek Jr
Affiliations

Helicobacter pylori genetic diversity within the gastric niche of a single human host

D A Israel et al. Proc Natl Acad Sci U S A. .

Abstract

Isolates of the gastric pathogen Helicobacter pylori harvested from different individuals are highly polymorphic. Strain variation also has been observed within a single host. To more fully ascertain the extent of H. pylori genetic diversity within the ecological niche of its natural host, we harvested additional isolates of the sequenced H. pylori strain J99 from its human source patient after a 6-year interval. Randomly amplified polymorphic DNA PCR and DNA sequencing of four unlinked loci indicated that these isolates were closely related to the original strain. In contrast, microarray analysis revealed differences in genetic content among all of the isolates that were not detected by randomly amplified polymorphic DNA PCR or sequence analysis. Several ORFs from loci scattered throughout the chromosome in the archival strain did not hybridize with DNA from the recent strains, including multiple ORFs within the J99 plasticity zone. In addition, DNA from the recent isolates hybridized with probes for ORFs specific for the other fully sequenced H. pylori strain 26695, including a putative traG homolog. Among the additional J99 isolates, patterns of genetic diversity were distinct both when compared with each other and to the original prototype isolate. These results indicate that within an apparently homogeneous population, as determined by macroscale comparison and nucleotide sequence analysis, remarkable genetic differences exist among single-colony isolates of H. pylori. Direct evidence that H. pylori has the capacity to lose and possibly acquire exogenous DNA is consistent with a model of continuous microevolution within its cognate host.

PubMed Disclaimer

Figures

Figure 1
Figure 1
RAPD PCR analysis of recent and archival H. pylori J99 isolates from the original human source patient. RAPD PCR patterns of 10 representative recent isolates and the archival J99 strain are shown. PCR was performed with primers D11344 and 14307, and products were analyzed by agarose gel electrophoresis. Results for corpus samples C1–C10 are shown in lanes 1–10, respectively, and results for the archival strain are indicated.
Figure 2
Figure 2
Absence and presence of ORFs in recent J99 isolates as determined by microarray analysis. Representative isolates C10, C3, and C6 were compared with archival J99 by whole-genome microarray analysis. The presence (red) or absence (black) of genes is displayed according to their position on the chromosome for each isolate (missing data are gray). (A) The ORFs of archival J99 are represented vertically in chromosomal order. (Left) The entire chromosome starting at JHP0001. (Right) An enlarged image showing a region of contiguous ORFs within the J99 plasticity zone missing in isolate C10. (B) Variably present ORFs specific to H. pylori strain 26695. (Left) All of the 26695 ORFs not present in sequenced strain J99. The red ORFs shown in the archival J99 lane are indicative of false positive hybridization. (Right) An enlarged image showing a region of linked ORFs present in all three recent J99 isolates.
Figure 3
Figure 3
Identification of an insertion sequence between JHP0929 and JHP0930 in recent isolates. (A) PCR products generated by amplification with primers within JHP0929 and JHP0931 were analyzed by agarose gel electrophoresis. MW, 1-kb ladder (Promega); lane 1, J99-archival; lane 2, C3; lane 3, C6; lane 4, C10; lane 5, negative control. (B) Location of insertion as determined by sequence analysis is indicated between ORFs JHP0929 and JHP0930.
Figure 4
Figure 4
Presence of variable loci among a population of recent J99 isolates (n = 13). The presence of loci that varied between the archival and recent J99 isolates as determined by microarray analysis are shown. Black bars represent the percentage of recent J99 isolates that possess ORFs present in the archival J99 and gray bars indicate the percentage of recent isolates that have DNA with homology to 26695-specific genes.
Figure 5
Figure 5
Relatedness of archival and recent J99 isolates as compared with each other and to independent H. pylori strains. Cluster analysis of microarray data for J99 isolates and 14 unrelated strains (26) shows that all J99 isolates cluster together on a branch distinct from other isolates.
See this image and copyright information in PMC

References

    1. Blaser M J, Perez-Perez G I, Kleanthous H, Cover T L, Peek R M, Chyou P H, Stemmermann G N, Nomura A. Cancer Res. 1995;55:2111–2115. - PubMed
    1. Nomura A, Stemmermann G N, Chyou P H, Kato I, Pérez-Pérez G I, Blaser M J. N Engl J Med. 1991;325:1132–1136. - PubMed
    1. Parsonnet J, Friedman G D, Vandersteen D P, Chang Y, Vogelman J H, Orentreich N, Sibley R K. N Engl J Med. 1991;325:1127–1131. - PubMed
    1. Peterson W L. N Engl J Med. 1991;324:1043–1048. - PubMed
    1. Taylor D N, Blaser M J. Epidemiol Rev. 1991;13:42–59. - PubMed

Publication types

MeSH terms

Associated data