Coordination of capsule assembly and cell wall biosynthesis in Staphylococcus aureus

Marvin Rausch, Julia P. Deisinger, Hannah Ulm, Anna Müller, Wenjin Li, Patrick Hardt, Xiaogang Wang, Xue Li, Marc Sylvester, Marianne Engeser, Waldemar Vollmer, Christa E. Müller, Hans Georg Sahl, Jean Claire Lee and Tanja Schneider ()
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Marvin Rausch: University of Bonn
Julia P. Deisinger: University of Bonn
Hannah Ulm: University of Bonn
Anna Müller: University of Bonn
Wenjin Li: University of Bonn
Patrick Hardt: University of Bonn
Xiaogang Wang: Brigham and Women’s Hospital, Harvard Medical School
Xue Li: Brigham and Women’s Hospital, Harvard Medical School
Marc Sylvester: University of Bonn
Marianne Engeser: University of Bonn
Waldemar Vollmer: Newcastle University
Christa E. Müller: University of Bonn
Hans Georg Sahl: University of Bonn
Jean Claire Lee: Brigham and Women’s Hospital, Harvard Medical School
Tanja Schneider: University of Bonn

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract The Gram-positive cell wall consists of peptidoglycan functionalized with anionic glycopolymers, such as wall teichoic acid and capsular polysaccharide (CP). How the different cell wall polymers are assembled in a coordinated fashion is not fully understood. Here, we reconstitute Staphylococcus aureus CP biosynthesis and elucidate its interplay with the cell wall biosynthetic machinery. We show that the CapAB tyrosine kinase complex controls multiple enzymatic checkpoints through reversible phosphorylation to modulate the consumption of essential precursors that are also used in peptidoglycan biosynthesis. In addition, the CapA1 activator protein interacts with and cleaves lipid-linked CP precursors, releasing the essential lipid carrier undecaprenyl-phosphate. We further provide biochemical evidence that the subsequent attachment of CP is achieved by LcpC, a member of the LytR-CpsA-Psr protein family, using the peptidoglycan precursor native lipid II as acceptor substrate. The Ser/Thr kinase PknB, which can sense cellular lipid II levels, negatively controls CP synthesis. Our work sheds light on the integration of CP biosynthesis into the multi-component Gram-positive cell wall.

Date: 2019
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DOI: 10.1038/s41467-019-09356-x

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