Helicobacter pylori DprA alleviates restriction barrier for incoming DNA

Abstract

Helicobacter pylori is a Gram-negative bacterium that colonizes human stomach and causes gastric inflammation. The species is naturally competent and displays remarkable diversity. The presence of a large number of restriction–modification (R–M) systems in this bacterium creates a barrier against natural transformation by foreign DNA. Yet, mechanisms that protect incoming double-stranded DNA (dsDNA) from restriction enzymes are not well understood. A DNA-binding protein, DNA Processing Protein A (DprA) has been shown to facilitate natural transformation of several Gram-positive and Gram-negative bacteria by protecting incoming single-stranded DNA (ssDNA) and promoting RecA loading on it. However, in this study, we report that H. pylori DprA (HpDprA) binds not only ssDNA but also dsDNA thereby conferring protection to both from various exonucleases and Type II restriction enzymes. Here, we observed a stimulatory role of HpDprA in DNA methylation through physical interaction with methyltransferases. Thus, HpDprA displayed dual functional interaction with H. pylori R–M systems by not only inhibiting the restriction enzymes but also stimulating methyltransferases. These results indicate that HpDprA could be one of the factors that modulate the R–M barrier during inter-strain natural transformation in H. pylori.

Long Noncoding RNA GAPLINC Regulates CD44-Dependent Cell Invasiveness and Associates with Poor Prognosis of Gastric Cancer

“…To improve gastric cancer early diagnosis and targeted therapy, an in-depth understanding of molecular underpinnings of the disease is required (3)(4)(5). It is of clinical importance to identify genes that contribute to gastric cancer development and present predictive value for diagnosis or prognosis (6)(7)(8).…”

Sequence Divergence and Conservation in Genomes of Helicobacter cetorum Strains from a Dolphin and a Whale

“…The comB -encoded type IV secretion system is used in recipient cells to facilitate DNA transfer by bacterial conjugation [52]. DprA protein binds DNA and can help protect it from restriction and stimulate its methylation [53].…”

Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles

“…RM systems comprise different combinations of endonuclease, methylase, and DNA specificity domains that use specific methylation patterns to label endogenous ''self'' genomic DNA, whereas unmodified exogenous DNA is recognized as ''non-self'' and subsequently cleaved and destroyed (Ershova et al 2012;Makarova et al 2013). Studies have proposed that RM systems can act as barriers to horizontal gene transfer (Waldron and Lindsay 2006;Hoskisson and Smith 2007;Dwivedi et al 2013). However, a role for RM systems in restricting intraspecies recombination is less well described (Waldron and Lindsay 2006).…”