Dataset Information

Repeat-associated plasticity in the Helicobacter pylori RD gene family.

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.

SUBMITTER: Shak JR

PROVIDER: S-EPMC2772487 | biostudies-other | 2009 Nov

REPOSITORIES: biostudies-other

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Repeat-associated plasticity in the Helicobacter pylori RD gene family.

Shak Joshua R JR Dick Jonathan J JJ Meinersmann Richard J RJ Perez-Perez Guillermo I GI Blaser Martin J MJ

Journal of bacteriology 20090911 22

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 conser ...[more]

PMID: 19749042

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Project description:Anaplasmosis, the most prevalent tick-transmitted disease of cattle, is caused by the rickettsial intracellular parasite Anaplasma marginale. The pathogen replicates within a parasitophorous vacuole formed from the invagination of the erythrocyte membrane. Several strains of A. marginale form "tails" or "appendages" which are attached to, and extend out from, the cytoplasmic side of the parasitophorous vacuole. Genomic analysis of the parasite antigen distributed along the appendage led to the discovery of the aaap (Anaplasma appendage associated protein) gene family located within a highly plastic region in the genome. The aaap gene family consists of aaap and several alps (for aaap-like proteins), depending on the strain. These genes/proteins are characterized by repeat sequences. To investigate locus plasticity, different versions of the locus were cloned from the same strain as well as from different strains, sequenced and aligned to identify changes. Our findings show that repeat sequences both within and between genes facilitated rearrangement events within the locus. Structural variation of the locus in the St. Maries strain was further investigated during infection of different cellular environments, i.e., bovine erythrocytes and tick cells, with a reduction in subpopulations of the aaap locus within the tick as compared to erythrocytes. Interestingly, subpopulations bearing alternative locus structures began to arise again when the pathogen was transferred from the tick environment into a naïve calf. Additionally, the Aaap protein expression profile between blood and tick samples showed a regulatory shift, indicating a host-specific response. Alignment of the protein sequences from different species of Anaplasma reveals six similar repeating motifs that appear to be unique to a few species of Anaplasma. The role the aaap locus may play in the pathogenesis of the bovine host or in tick infection/transmission remains unknown; however, the changes in aaap locus subpopulations, locus structure, and protein expression indicate that these genes have a role in strain diversification.

Dataset Information

Repeat-associated plasticity in the Helicobacter pylori RD gene family.

Publications

Repeat-associated plasticity in the Helicobacter pylori RD gene family.

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