Genes required for glycolipid synthesis and lipoteichoic acid anchoring in Staphylococcus aureus.
Staphylococcus aureus lipoteichoic acid (LTA) is composed of a linear 1,3-linked polyglycerolphosphate chain and is tethered to the bacterial membrane by a glycolipid (diglucosyl-diacylglycerol [Glc2-DAG]). Glc2-DAG is synthesized in the bacterial cytoplasm by YpfP, a processive enzyme that transfers glucose to diacylglycerol (DAG), using UDP-glucose as its substrate. Here we present evidence that the S. aureus alpha-phosphoglucomutase (PgcA) and UTP:alpha-glucose 1-phosphate uridyltransferase (GtaB) homologs are required for the synthesis of Glc2-DAG. LtaA (lipoteichoic acid protein A), a predicted membrane permease whose structural gene is located in an operon with ypfP, is not involved in Glc2-DAG synthesis but is required for synthesis of glycolipid-anchored LTA. Our data suggest a model in which LtaA facilitates the transport of Glc2-DAG from the inner (cytoplasmic) leaflet to the outer leaflet of the plasma membrane, delivering Glc2-DAG as a substrate for LTA synthesis, thereby generating glycolipid-anchored LTA. Glycolipid anchoring of LTA appears to play an important role during infection, as S. aureus variants lacking ltaA display defects in the pathogenesis of animal infections.
Gründling
Angelika
A
Department of Microbiology, 920 East 58th Street, Chicago, IL 60637, USA.
Schneewind
Olaf
O
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D015964:Gene Expression Regulation, Bacterial; D006017:Glycolipids / Q000096:biosynthesis*; D006801:Humans; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010733:Phosphoglucomutase / Q000235:genetics / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D013682:Teichoic Acids / Q000096:biosynthesis*; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D006017:Glycolipids; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D013682:Teichoic Acids; C009900:lipoteichoic acid; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase; D010733:Phosphoglucomutase