Repeat-associated Plasticity in the Helicobacter Pylori RD Gene Family

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 2009 Sep 15

PMID 19749042

Citations 8

Authors

Joshua R Shak

Jonathan J Dick

Richard J Meinersmann

Guillermo I Perez-Perez

Martin J Blaser

Affiliations

Soon will be listed here.

Abstract

The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3' region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host.

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References

Aras R, Kang J, Tschumi A, Harasaki Y, Blaser M . Extensive repetitive DNA facilitates prokaryotic genome plasticity. Proc Natl Acad Sci U S A. 2003; 100(23):13579-84. PMC: 263856. DOI: 10.1073/pnas.1735481100. View

Bichara M, Wagner J, Lambert I . Mechanisms of tandem repeat instability in bacteria. Mutat Res. 2006; 598(1-2):144-63. DOI: 10.1016/j.mrfmmm.2006.01.020. View

Wirth H, Yang M, Peek Jr R, Hook-Nikanne J, Fried M, Blaser M . Phenotypic diversity in Lewis expression of Helicobacter pylori isolates from the same host. J Lab Clin Med. 1999; 133(5):488-500. DOI: 10.1016/s0022-2143(99)90026-4. View

Blanchard T, Czinn S, Nedrud J . Host response and vaccine development to Helicobacter pylori infection. Curr Top Microbiol Immunol. 1999; 241:181-213. DOI: 10.1007/978-3-642-60013-5_10. View

Merrell D, Goodrich M, Otto G, Tompkins L, Falkow S . pH-regulated gene expression of the gastric pathogen Helicobacter pylori. Infect Immun. 2003; 71(6):3529-39. PMC: 155744. DOI: 10.1128/IAI.71.6.3529-3539.2003. View

Perez-Perez G, Sack R, Reid R, Santosham M, Croll J, Blaser M . Transient and persistent Helicobacter pylori colonization in Native American children. J Clin Microbiol. 2003; 41(6):2401-7. PMC: 156565. DOI: 10.1128/JCM.41.6.2401-2407.2003. View

Lovett S . Encoded errors: mutations and rearrangements mediated by misalignment at repetitive DNA sequences. Mol Microbiol. 2004; 52(5):1243-53. DOI: 10.1111/j.1365-2958.2004.04076.x. View

Moxon R, Bayliss C, Hood D . Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu Rev Genet. 2006; 40:307-33. DOI: 10.1146/annurev.genet.40.110405.090442. View

Felsenstein J . CONFIDENCE LIMITS ON PHYLOGENIES: AN APPROACH USING THE BOOTSTRAP. Evolution. 2017; 39(4):783-791. DOI: 10.1111/j.1558-5646.1985.tb00420.x. View

10.

Delahay R, Balkwill G, Bunting K, Edwards W, Atherton J, Searle M . The highly repetitive region of the Helicobacter pylori CagY protein comprises tandem arrays of an alpha-helical repeat module. J Mol Biol. 2008; 377(3):956-71. PMC: 2581425. DOI: 10.1016/j.jmb.2008.01.053. View

11.

Pflock M, Finsterer N, Joseph B, Mollenkopf H, Meyer T, Beier D . Characterization of the ArsRS regulon of Helicobacter pylori, involved in acid adaptation. J Bacteriol. 2006; 188(10):3449-62. PMC: 1482845. DOI: 10.1128/JB.188.10.3449-3462.2006. View

12.

Kihara D, Kanehisa M . Tandem clusters of membrane proteins in complete genome sequences. Genome Res. 2000; 10(6):731-43. DOI: 10.1101/gr.10.6.731. View

13.

LARKIN M, Blackshields G, Brown N, Chenna R, McGettigan P, McWilliam H . Clustal W and Clustal X version 2.0. Bioinformatics. 2007; 23(21):2947-8. DOI: 10.1093/bioinformatics/btm404. View

14.

Kondrashov F, Kondrashov A . Role of selection in fixation of gene duplications. J Theor Biol. 2005; 239(2):141-51. DOI: 10.1016/j.jtbi.2005.08.033. View

15.

Apic G, Gough J, Teichmann S . Domain combinations in archaeal, eubacterial and eukaryotic proteomes. J Mol Biol. 2001; 310(2):311-25. DOI: 10.1006/jmbi.2001.4776. View

16.

Rubinsztein-Dunlop S, Guy B, Lissolo L, Fischer H . Identification of two new Helicobacter pylori surface proteins involved in attachment to epithelial cell lines. J Med Microbiol. 2005; 54(Pt 5):427-434. DOI: 10.1099/jmm.0.45921-0. View

17.

Romero D, Martinez-Salazar J, Ortiz E, Rodriguez C, Valencia-Morales E . Repeated sequences in bacterial chromosomes and plasmids: a glimpse from sequenced genomes. Res Microbiol. 2000; 150(9-10):735-43. DOI: 10.1016/s0923-2508(99)00119-9. View

18.

Peek Jr R, Blaser M . Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002; 2(1):28-37. DOI: 10.1038/nrc703. View

19.

Nilsson C, Skoglund A, Moran A, Annuk H, Engstrand L, Normark S . An enzymatic ruler modulates Lewis antigen glycosylation of Helicobacter pylori LPS during persistent infection. Proc Natl Acad Sci U S A. 2006; 103(8):2863-8. PMC: 1413829. DOI: 10.1073/pnas.0511119103. View

20.

Romero-Gallo J, Perez-Perez G, Novick R, Kamath P, Norbu T, Blaser M . Responses of endoscopy patients in Ladakh, India, to Helicobacter pylori whole-cell and Cag A antigens. Clin Diagn Lab Immunol. 2002; 9(6):1313-7. PMC: 130106. DOI: 10.1128/cdli.9.6.1313-1317.2002. View