Sau1: a Novel Lineage-Specific Type I Restriction-Modification System That Blocks Horizontal Gene Transfer into Staphylococcus aureus and between S. aureus Isolates of Different Lineages

The Sau1 type I restriction-modification system is found on the chromosome of all nine sequenced strains ofStaphylococcus aureus and includes a singlehsdR (restriction) gene and two copies ofhsdM (modification) andhsdS (sequence specificity) genes. The strainS. aureus RN4220 is a vital intermediate for laboratoryS. aureus manipulation, as it can accept plasmid DNA fromEscherichia coli . We show that it carries a mutation in thesau1hsdR gene and that complementation restored a nontransformable phenotype. Sau1 was also responsible for reduced conjugative transfer from enterococci, a model of vancomycin resistance transfer. This may explain why only four vancomycin-resistantS. aureus strains have been identified despite substantial selective pressure in the clinical setting. Using a multistrainS. aureus microarray, we show that the two copies of sequence specificity genes (sau1hsdS1 andsau1hsdS2 ) vary substantially between isolates and that the variation corresponds to the 10 dominantS. aureus lineages. Thus, RN4220 complemented withsau1hsdR was resistant to bacteriophage lysis but only if the phage was grown onS. aureus of a different lineage. Similarly, it could be transduced with DNA from its own lineage but not with the phage grown on differentS. aureus lineages. Therefore, we propose that Sau1 is the major mechanism for blocking transfer of resistance genes and other mobile genetic elements intoS. aureus isolates from other species, as well as for controlling the spread of resistance genes between isolates of differentS. aureus lineages. Blocking Sau1 should also allow genetic manipulation of clinical strains ofS. aureus .