The function of CozE proteins is linked to lipoteichoic acid biosynthesis in Staphylococcus aureus .

Autor: Barbuti MD; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway., Lambert E; Biozentrum, University of Basel, Basel, Switzerland., Myrbråten IS; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway., Ducret A; Molecular Microbiology and Structural Biochemistry, CNRS UM 5086, Université de Lyon, Lyon, France., Stamsås GA; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway., Wilhelm L; Molecular Microbiology and Structural Biochemistry, CNRS UM 5086, Université de Lyon, Lyon, France., Liu X; Department of Pathogen, Biology, International Cancer Center, Shenzhen University Medical School, Shenzhen, Guangdong, China.; Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland., Salehian Z; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway., Veening J-W; Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland., Straume D; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway., Grangeasse C; Molecular Microbiology and Structural Biochemistry, CNRS UM 5086, Université de Lyon, Lyon, France., Perez C; Biozentrum, University of Basel, Basel, Switzerland.; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, USA., Kjos M; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
Jazyk: angličtina
Zdroj: MBio [mBio] 2024 Jun 12; Vol. 15 (6), pp. e0115724. Date of Electronic Publication: 2024 May 17.
DOI: 10.1128/mbio.01157-24
Abstrakt: Coordinated membrane and cell wall synthesis is vital for maintaining cell integrity and facilitating cell division in bacteria. However, the molecular mechanisms that underpin such coordination are poorly understood. Here we uncover the pivotal roles of the staphylococcal proteins CozEa and CozEb, members of a conserved family of membrane proteins previously implicated in bacterial cell division, in the biosynthesis of lipoteichoic acids (LTA) and maintenance of membrane homeostasis in Staphylococcus aureus . We establish that there is a synthetic lethal relationship between CozE and UgtP, the enzyme synthesizing the LTA glycolipid anchor Glc 2 DAG. By contrast, in cells lacking LtaA, the flippase of Glc 2 DAG, the essentiality of CozE proteins was alleviated, suggesting that the function of CozE proteins is linked to the synthesis and flipping of the glycolipid anchor. CozE proteins were indeed found to modulate the flipping activity of LtaA in vitro . Furthermore, CozEb was shown to control LTA polymer length and stability. Together, these findings establish CozE proteins as novel players in membrane homeostasis and LTA biosynthesis in S. aureus .IMPORTANCELipoteichoic acids are major constituents of the cell wall of Gram-positive bacteria. These anionic polymers are important virulence factors and modulators of antibiotic susceptibility in the important pathogen Staphylococcus aureus . They are also critical for maintaining cell integrity and facilitating proper cell division. In this work, we discover that a family of membrane proteins named CozE is involved in the biosynthesis of lipoteichoic acids (LTAs) in S. aureus . CozE proteins have previously been shown to affect bacterial cell division, but we here show that these proteins affect LTA length and stability, as well as the flipping of glycolipids between membrane leaflets. This new mechanism of LTA control may thus have implications for the virulence and antibiotic susceptibility of S. aureus .
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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