title: The capsular polysaccharide of Staphylococcus aureus is attached to peptidoglycan by the LytR-CpsA-Psr (LCP) family of enzymes.
abstract: Envelope biogenesis in bacteria involves synthesis of intermediates that are tethered to the lipid carrier undecaprenol-phosphate. LytR-CpsA-Psr (LCP) enzymes have been proposed to catalyze the transfer of undecaprenol-linked intermediates onto the C6-hydroxyl of MurNAc in peptidoglycan, thereby promoting attachment of wall teichoic acid (WTA) in bacilli and staphylococci and capsular polysaccharides (CPS) in streptococci. S. aureus encodes three lcp enzymes, and a variant lacking all three genes (Δlcp) releases WTA from the bacterial envelope and displays a growth defect. Here, we report that the type 5 capsular polysaccharide (CP5) of Staphylococcus aureus Newman is covalently attached to the glycan strands of peptidoglycan. Cell wall attachment of CP5 is abrogated in the Δlcp variant, a defect that is best complemented via expression of lcpC in trans. CP5 synthesis and peptidoglycan attachment are not impaired in the tagO mutant, suggesting that CP5 synthesis does not involve the GlcNAc-ManNAc linkage unit of WTA and may instead utilize another Wzy-type ligase to assemble undecaprenyl-phosphate intermediates. Thus, LCP enzymes of S. aureus are promiscuous enzymes that attach secondary cell wall polymers with discrete linkage units to peptidoglycan.
authors.affiliation: From the Department of Microbiology, University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Yvonne Gar-Yun
authors.initials: YG
authors.lastname: Chan
authors.affiliation: From the Department of Microbiology, University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Hwan Keun
authors.initials: HK
authors.lastname: Kim
authors.affiliation: From the Department of Microbiology, University of Chicago, Chicago, Illinois 60637 and the Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Argonne, Illinois 60439.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.affiliation: From the Department of Microbiology, University of Chicago, Chicago, Illinois 60637 and the Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Argonne, Illinois 60439 dmissiak@bsd.uchicago.edu.
authors.forename: Dominique
authors.initials: D
authors.lastname: Missiakas
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D005260:Female; D006867:Hydrolases / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism*; D010457:Peptidoglycan / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D013211:Staphylococcus aureus / Q000201:enzymology*; D013379:Substrate Specificity; D013682:Teichoic Acids / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000906:Antibodies; D001426:Bacterial Proteins; C093500:LytR protein, Staphylococcus aureus; D010457:Peptidoglycan; D011134:Polysaccharides; D013682:Teichoic Acids; D014157:Transcription Factors; D006867:Hydrolases; D008025:Ligases
keywords: Capsular Polysaccharide; Carbohydrate Biosynthesis; Cell Wall; Hydrolase; LytR-CpsA-Psr; Peptidoglycan; Staphylococcus aureus (S. aureus); Teichoic Acid; Undecaprenol
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