Comprehensive functional genomics reveals Staphylococcus epidermidis restriction modification system diversity compared to conservation in Staphylococcus aureus

Staphylococcus epidermidis is a major cause of hospital-acquired infections, especially those related to implanted medical devices. Understanding how S. epidermidis causes disease and ways to combat these infections have been hindered by an inability to genetically manipulate the “hospital-adapted” strains that cause clinical disease. Here we provide the first comprehensive analyses of the mechanisms by which S. epidermidis resists the uptake of foreign DNA and demonstrate these to be distinct to those described for S. aureus, that until now had been assumed to be the same. Using these insights, we demonstrate an efficient approach for the genetic manipulation of S. epidermidis to enable the study of clinically relevant isolates for the first time.