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DprB facilitates inter- and intragenomic recombination in Helicobacter pylori.

ABSTRACT: For naturally competent microorganisms, such as Helicobacter pylori, the steps that permit recombination of exogenous DNA are not fully understood. Immediately downstream of an H. pylori gene (dprA) that facilitates high-frequency natural transformation is HP0334 (dprB), annotated to be a putative Holliday junction resolvase (HJR). We showed that the HP0334 (dprB) gene product facilitates high-frequency natural transformation. We determined the physiologic roles of DprB by genetic analyses. DprB controls in vitro growth, survival after exposure to UV or fluoroquinolones, and intragenomic recombination. dprB ruvC double deletion dramatically decreases both homologous and homeologous transformation and survival after exposure to DNA-damaging agents. Moreover, the DprB protein binds to synthetic Holliday junction structures rather than double-stranded or single-stranded DNA. These results demonstrate that the dprB product plays important roles affecting inter- and intragenomic recombination. We provide evidence that the two putative H. pylori HJRs (DprB and RuvC) have overlapping but distinct functions involving intergenomic (primarily DprB) and intragenomic (primarily RuvC) recombination.

SUBMITTER: Zhang XS

PROVIDER: S-EPMC3416544 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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DprB facilitates inter- and intragenomic recombination in Helicobacter pylori.

Zhang Xue-Song XS Blaser Martin J MJ

Journal of bacteriology 20120518 15

For naturally competent microorganisms, such as Helicobacter pylori, the steps that permit recombination of exogenous DNA are not fully understood. Immediately downstream of an H. pylori gene (dprA) that facilitates high-frequency natural transformation is HP0334 (dprB), annotated to be a putative Holliday junction resolvase (HJR). We showed that the HP0334 (dprB) gene product facilitates high-frequency natural transformation. We determined the physiologic roles of DprB by genetic analyses. DprB ...[more]

PMID: 22609923

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Project description:BackgroundHelicobacter pylori is a human stomach pathogen, naturally-competent for DNA uptake, and prone to homologous recombination. Extensive homoplasy (i.e., phylogenetically-unlinked identical variations) observed in H. pylori genes is considered a hallmark of such recombination. However, H. pylori also exhibits a high mutation rate. The relative adaptive role of homologous recombination and mutation in species diversity is a highly-debated issue in biology. Recombination results in homoplasy. While convergent mutation can also account for homoplasy, its contribution is thought to be minor. We demonstrate here that, contrary to dogma, convergent mutation is a key contributor to Helicobacter pylori homoplasy, potentially driven by adaptive evolution of proteins.ResultsOur present genome-wide analysis shows that homoplastic nonsynonymous (amino acid replacement) changes are not typically accompanied by homoplastic synonymous (silent) variations. Moreover, the majority of the codon positions with homoplastic nonsynonymous changes also contain different (i.e. non-homoplastic) nonsynonymous changes arising from mutation only. This indicates that, to a considerable extent, nonsynonymous homoplasy is due to convergent mutations. High mutation rate or limited availability of evolvable sites cannot explain this excessive convergence, as suggested by our simulation studies. Rather, the genes with convergent mutations are overrepresented in distinct functional categories, suggesting possible selective responses to conditions such as distinct micro-niches in single hosts, and to differences in host genotype, physiology, habitat and diet.ConclusionsWe propose that mutational convergence is a key player in H. pylori's adaptation and extraordinary persistence in human hosts. High frequency of mutational convergence could be due to saturation of evolvable sites capable of responding to selection pressures, while the number of mutable residues is far from saturation. We anticipate a similar scenario of mutational vs. recombinational genome dynamics or plasticity for other naturally competent microbes where strong positive selection could favor frequent convergent mutations in adaptive protein evolution.

Project description:Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of Evodia rutaecarpa, evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against H. pylori is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on H. pylori growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on H. pylori-induced inflammation were investigated in vitr. Results of this study showed the growth of the H. pylori reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expressions of replication and transcription machineries of H. pylori. Treatment of evodiamine also induced downregulation of urease and diminished translocation of cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) proteins into gastric adenocarcinoma (AGS) cells. This may be resulted from the reduction of CagA and VacA expressions as well as the type IV secretion system (T4SS) components and secretion system subunit protein A (SecA) protein which are involved in translocation of CagA and VacA into host cells, respectively. In particular, evodiamine inhibited the activation of signaling proteins such as the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway induced by H. pylori infection. It consequently might contribute to reduction of interleukin (IL)-8 production in AGS cells. Collectively, these results suggest anti-bacterial and anti-inflammatory effects of evodiamine against H. pylori.

Dataset Information

DprB facilitates inter- and intragenomic recombination in Helicobacter pylori.

Publications

DprB facilitates inter- and intragenomic recombination in Helicobacter pylori.

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