A new paper in PLOS Pathogens demonstrates that the human pathogen Streptococcus pneumoniae (one of the causes of bacterial pneumonia) possesses an unusual enzyme that protects foreign DNA taken up during transformation, allowing exchange of pathogenicity islands donated from other pathogenic bacteria.
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 genetic transformation, thus allows for vaccine evasion. Natural genetic transformation 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 DNA sequences. The researchers found that the role of DpnA is to protect foreign DNA, allowing pathogenicity island exchange between bacteria.
Programmed Protection of Foreign DNA from Restriction Allows Pathogenicity IslandExchange during Pneumococcal Transformation. (2013) PLoS Pathog 9(2): e1003178. doi:10.1371/journal.ppat.1003178
Natural genetic transformation can compensate for the absence of sexual reproduction in bacteria, allowing genetic diversification by recombination. It proceeds through the internalization of single stranded (ss) DNA fragments created from an exogenous double stranded (ds) DNA substrate, which are incorporated into the genome by homology. On the other hand, restriction- modification (R-M) systems, which protect bacteria from bacteriophage attack by degrading invading foreign DNA, potentially antagonize transformation. About half of the strains of the naturally transformable species and human pathogen Streptococcus pneumoniae possess an R-M system, DpnII, restricting unmethylated dsDNA. DpnII strains possess DpnA which is unusual in that it methylates ssDNA. Here we show that DpnA plays a crucial role in the protection of internalized heterologous transforming ssDNA, preventing the post-replicative destruction by DpnII of transformants produced by chromosomal inte- gration of heterogolous DNA by virtue of flanking homology. This protective role of DpnA is of particular importance for acquisition of pathogenicity islands, such as capsule loci, from non-DpnII origin by DpnII strains, likely contributing to pneumococcal virulence via escape from capsule-based vaccines. More generally, this finding is the first evidence for a mechanism that actively promotes genetic diversity of S. pneumoniae through active protection and incorporation of foreign DNA.