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

Autor:	Bonini D; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom., Duggan S; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.; MRC Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom., Alnahari A; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.; Department of Biological Sciences, University of Jeddah, Jeddah, Saudi Arabia., Brignoli T; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Strahl H; Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Massey RC; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.; School of Microbiology, University College Cork, Cork, Ireland.; APC Microbiome Ireland, University College Cork, Cork, Ireland.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2024 Aug 14; Vol. 15 (8), pp. e0151224. Date of Electronic Publication: 2024 Jul 22.
DOI:	10.1128/mbio.01512-24
Abstrakt:	Staphylococcus aureus produces a plethora of virulence factors critical to its ability to establish an infection and cause disease. We have previously characterized a small membrane protein, MspA, which has pleiotropic effects 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 enzymes involved in LTA biosynthesis (LtaA, LtaS, UgtP, and SpsB), interfering with their normal activities. MspA, in particular, interacts with the type I signal peptidase SpsB, limiting its cleavage of LtaS into its active form. These findings suggest that MspA contributes to maintaining a physiological level of LTA in the cell wall by interacting with and inhibiting the activity of SpsB, thereby uncovering a critical role for the MspA protein in regulating cell envelope biosynthesis and pathogenicity.IMPORTANCEThe S. aureus cell envelope, comprising 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, an 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 suggest that MspA represents a promising target for the development of future therapeutic strategies. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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