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Streptococcus pneumonia Shields Foreign DNA Derived From Other Bacteria To Promote Genetic Diversity And Vaccine Evasion

A new report demonstrates that the human pathogen Streptococcus (S.) pneumoniae (one of the known causes of ) possesses an unusual enzyme that protects foreign taken up during transformation, allowing exchange of pathogenicity islands donated from other . This study, published in the Open Access journal PLOS Pathogens by researchers from the Laboratory of Microbiology and Molecular Genetics (CNRS-Université , Toulouse, France), establishes a role for this enzyme in protecting internalized DNA from restriction, and simultaneously shows that S. pneumoniae uses transformation, for example by DNA picked up from other bacterial strains, specifically to promote genome diversification.

Exchange of pathogenicity islands is crucial for pneumococcal virulence, as illustrated by the impressive variability in the polysaccharide capsule, which is usually targeted by current vaccines. Acquisition of different capsule loci, by relying on this , thus allows for vaccine evasion. Natural is thought of as the bacterial equivalent of sexual reproduction, allowing intra- and inter-species genetic exchange. This process, involving uptake of foreign DNA as single-strands (ss) that leads to chromosomal integration, is transient in S. pneumoniae.

Restriction-modification (R-M) systems classically include a restrictase, which protects the host bacteria from attack by bacteriophage via the degradation of only the foreign double-stranded (ds) DNA, and a dsDNA methylase that methylates the host genome, providing self-immunity against this restrictase. Since they degrade only foreign DNA, R-M systems are proposed to antagonize transformation by DNA from other bacteria. The DpnII R-M system investigated in this study is present in around half of pneumococcal isolates tested and also possesses an unusual methylase of ssDNA, DpnA, which is specifically induced during the brief genetic transformation time window.

This study shows that DpnA gene is crucial for the exchange of pathogenicity islands when the foreign DNA is unmethylated (i.e., from a non-DpnII modified DNA donor). By methylating the internalized foreign ssDNA, DpnA protects the chromosome of those transformants that incorporate the foreign pathogenicity islands, such as the capsule locus. In the absence of this unique methylation, the novel transformant chromosomes would be degraded by the DpnII restrictase, thus forbidding the acceptance of the foreign .

The researchers found that the role of DpnA is to protect foreign DNA, allowing pathogenicity island exchange between bacteria. Jean-Pierre Claverys, Principal Investigator and senior author of the paper concludes that “this finding is the first evidence for a mechanism that actively promotes genetic diversity of S. pneumoniae through programmed protection and incorporation of foreign DNA.”


FINANCIAL DISCLOSURE: CJ was funded by a grant from the Agence Nationale de la Recherche (projet n_ BLAN06-3_141806). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTEREST: The authors have declared that no competing interests exist.
LINK TO THE PUBLISHED ARTICLE: http://dx.plos.org/10.1371/journal.ppat.1003178
CITATION: Johnston C, Martin B, Granadel C, Polard P, Claverys J-P (2013) Programmed Protection of Foreign DNA from Restriction Allows Pathogenicity Island Exchange during Pneumococcal Transformation. PLoS Pathog 9(2): e1003178. doi:10.1371/journal.ppat.1003178
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