The Type I Restriction Modification System SpnIII of Streptococcus pneumoniae

The phase variable expression of alternative specificity subunits by the type I restriction modification system SpnIII has been proven to differentially regulate important virulence factors. These gene expression differences are envisaged to translate into significant differences in the virulence of strains, dominated by different specificity subunits, in murine models of infection. The presence of this type I system in the core pneumococcal genome hints at a conserved, global mechanism of regulation, including that of virulence. The use of wildtype strains enriched in alternative specificity subunits has revealed that recombination within the spnIII locus is not reciprocal and is highly variable between strains. Despite this variability, methylation of the genome by different SpnIII variants results in differential gene expression and significant differences in models of invasive disease. The recombination within the spnIII locus appears to be much more complex than similar, previously reported systems. Recombination is not mediated by the classical homologous recombination pathways but is partially controlled by a site specific tyrosine recombinase. Investigations into the impact of SpnIII may be capable of improving our understanding of how this nasopharyngeal coloniser is capable of causing devastating invasive disease.