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.
Highlights
The Gram-positive cell wall consists of peptidoglycan functionalized with anionic glycopolymers, such as wall teichoic acid and capsular polysaccharide (CP)
We provide biochemical evidence that the attachment of the anionic precursor likely occurs on the level of the lipid-linked peptidoglycan precursor lipid II, and is facilitated in the presence of CapA1, indicating its cooperative functioning with LCP proteins
Homology searches with CapD and CapN suggested that both proteins are involved in the synthesis of the first soluble capsule precursor UDP-D-FucNAc18
Summary
The Gram-positive cell wall consists of peptidoglycan functionalized with anionic glycopolymers, such as wall teichoic acid and capsular polysaccharide (CP). Hannah Ulm. Gram-positive bacteria is densely decorated with glycopolymers such as wall teichoic acid (WTA) and capsular polysaccharide (CP). In contrast to the biosyntheses of PG and WTA, for which the individual enzymatic reactions have already been characterized in vitro[2,3], the biochemistry underlying capsule formation in Gram-positive bacteria is not well understood. Even more so, it is largely unknown how the different cell wall synthesis pathways, which share building blocks and membrane carriers, function in a coordinated and integrated fashion. Among predominant methicillinresistant S. aureus clones worldwide are the CP8 + lineages ST1, ST30, ST59, ST80, and ST239 and the CP5 + lineages ST5 and ST22
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