Class III phase variation in Staphylococcus epidermidis: Staphylococcus epidermidis icaADBC(+) and icaADBC(-) human skin colonization: The Staphylococcus epidermidis two-component regulatory system sae

Phase (or phenotypic) variation is a relatively common phenomenon observed in bacteria. In pathogenic species this variation is often associated with the virulence of the organism. In general, phase variation refers to a reversible switch between an "all-or-none" (on/off) expressing phase. Additionally phase variation may be used to describe an irreversible change resulting from environmental regulation, selection or unidirectional mutation. This variety of phase variation in Staphylococcus epidermidis is called Class III phase variation and is due to the complete loss of a gene or multiple genes. This study demonstrates that this type of phase variation occurs in multiple "systems" or environments, including biofilm flow cells, static bacterial cultures, animal models and on human skin. It is also demonstrated that this phenomenon is due to homologous recombination and the presence of IS elements. Phase or phenotypic variation occurs readily both in vitro and in vivo and is often found in clinical strains of S. epidermidis. Previous studies have demonstrated that Staphylococcus epidermidis isolates colonizing the skin of healthy humans do not typically encode icaADBC, the genes responsible for the production of polysaccharide intercellular adhesin (PIA) or biofilm. It was therefore hypothesized that the presence of icaADBC was deleterious to the successful colonization of S. epidermidis on human skin. Using a human skin competition model, this study determined that 1457 was outcompeted at 1, 3, and 10 days by an isogenic icaADBC mutant (1457 ica::dhfr). The saeRS two-component regulatory system regulates transcription of multiple virulence factors in Staphylococcus aureus. This study demonstrated that the saePQRS region in Staphylococcus epidermidis is transcriptionally regulated in a temporal manner and is arranged in a manner similar to that previously described for S. aureus. Additionally, our studies demonstrate the role of sae in the switch from aerobic to anaerobic growth of S. epidermidis.