Investigating the Regulation of Fatty Acid Efflux Pump FarE by TetR Family Regulator FarR in Staphylococcus aureus
Abstract
The success of the USA300 strain of methicillin resistant Staphylococcus aureus can be attributed in part to its enhanced ability to overcome innate defenses of the skin including sebum, which provides a source of antimicrobial unsaturated free fatty acids (uFFA). We have previously identified farE and farR genes that confer S. aureus resistance to uFFA, respectively encoding a uFFA efflux pump and a TetR family regulator required for farE expression. However, the exact regulatory mechanism of FarR remains to be elucidated. Here, we show the importance of a conserved TAGWTTA motif in FarR operator sites, such that the loss of this motif in autoregulatory operator sites caused a de-repression of FarR. However, this de-repression did not cause an increase in resistance to uFFA. Additionally, we have identified the importance of cysteine residues for FarR function. These findings shed further light on the mechanisms of S. aureus resistance to antimicrobial uFFA.