Lipoteichoic acid biosynthesis by Staphylococcus aureus is controlled by the MspA protein through competitive interference.

Staphylococcus aureus produces a plethora of virulence factors critical to its ability to establish an infection and cause disease. We have previously characterised a small membrane protein, MspA, which has pleiotropic affects on virulence and contributes to S. aureus pathogenicity in vivo. Here we report that mspA inactivation triggers overaccumulation of the essential cell wall component lipoteichoic acid (LTA) which, in turn, decreases autolytic activity and leads to increased cell size due to a delay in cell separation. We show that MspA directly interacts with the LTA synthesis enzymes UgtP, LtaA and LtaS, and competitively interferes with the association between LtaA and LtaS. While complementation of the mspA mutant with wild-type mspA reduces the amount of LTA, expression of a mutated version of MspA that does not interfere with the interactions between LtaA and LtaS does not. We suggest that MspA contributes to maintaining a physiological level of LTA in the cell wall by interacting with the LTA synthetic enzymes. In conclusion, this study uncovers the critical role of the MspA protein in regulating cell envelope biosynthesis and pathogenicity. IMPORTANCEThe S. aureus cell envelope, comprising of the cytoplasmic membrane, a thick peptidoglycan layer and the anionic polymers lipoteichoic acid and wall teichoic acids, is fundamental for bacterial growth and division, as well as being the main interface between the pathogen and the host. It has become increasingly apparent that the synthesis and turnover of cell envelope components also affect the virulence of S. aureus. In this study, we show that MspA, a novel effector of S. aureus virulence, contributes to the maintenance of normal levels of lipoteichoic acid in the cell wall, with implications on cell cycle and size. These findings further our understanding of the connections between envelope synthesis and pathogenicity and suggests MspA as a novel a target for therapeutic intervention.