title: Two-enzyme systems for glycolipid and polyglycerolphosphate lipoteichoic acid synthesis in Listeria monocytogenes.
abstract: Lipoteichoic acid (LTA) is an important cell wall polymer in gram-positive bacteria and often consists a polyglycerolphosphate backbone chain that is linked to the membrane by a glycolipid. In Listeria monocytogenes this glycolipid is Gal-Glc-DAG or Gal-Ptd-6Glc-DAG. Using a bioinformatics approach, we have identified L. monocytogenes genes predicted to be involved in glycolipid (lmo2555 and lmo2554) and LTA backbone (lmo0644 and lmo0927) synthesis. LTA and glycolipid analysis of wild-type and mutant strains confirmed the function of Lmo2555 and Lmo2554 as glycosyltransferases required for the formation of Glc-DAG and Gal-Glc-DAG. Deletion of a third gene, lmo2553, located in the same operon resulted in the production of LTA with an altered structure. lmo0927 and lmo0644 encode proteins with high similarity to the staphylococcal LTA synthase LtaS, which is responsible for polyglycerolphosphate backbone synthesis. We show that both proteins are involved in LTA synthesis. Our data support a model whereby Lmo0644 acts as an LTA primase LtaP and transfers the initial glycerolphosphate onto the glycolipid anchor, and Lmo0927 functions as LTA synthase LtaS, which extends the glycerolphosphate backbone chain. Inactivation of LtaS leads to severe growth and cell division defects, underscoring the pivotal role of LTA in this gram-positive pathogen.
authors.affiliation: Department of Microbiology, Imperial College London, London, UK.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Webb
authors.forename: Maria
authors.initials: M
authors.lastname: Karatsa-Dodgson
authors.forename: Angelika
authors.initials: A
authors.lastname: Gründling
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000201:enzymology; D019295:Computational Biology; D005994:Glycerophosphates / Q000096:biosynthesis*; D006017:Glycolipids / Q000096:biosynthesis*; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D008089:Listeria monocytogenes / Q000201:enzymology* / Q000235:genetics; D013058:Mass Spectrometry; D009876:Operon; D013682:Teichoic Acids / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D005994:Glycerophosphates; D006017:Glycolipids; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C008964:polyglycerolphosphate; C009900:lipoteichoic acid; D016695:Glycosyltransferases
references.citation: J Biol Chem. 1999 Mar 26;274(13):8405-10
references.pmid: 10085071
references.citation: J Bacteriol. 1963 Sep;86:414-28
references.pmid: 14066417
references.citation: Science. 2001 Oct 26;294(5543):849-52
references.pmid: 11679669
references.citation: Biochim Biophys Acta. 1971 Sep 1;239(3):428-42
references.pmid: 5000277
references.citation: Mol Microbiol. 1997 Jul;25(2):285-94
references.pmid: 9282740
references.citation: Biochimie. 1992 Jul-Aug;74(7-8):705-11
references.pmid: 1391050
references.citation: Biochem J. 1997 Sep 15;326 ( Pt 3):929-39
references.pmid: 9334165
references.citation: Nature. 1983 Oct 20-26;305(5936):709-12
references.pmid: 6226876
references.citation: Gene. 1990 Sep 28;94(1):129-32
references.pmid: 2121618
references.citation: Mol Microbiol. 1998 Jul;29(2):419-30
references.pmid: 9720862
references.citation: J Bacteriol. 1986 Oct;168(1):115-22
references.pmid: 3093460
references.citation: Proc Natl Acad Sci U S A. 2007 May 15;104(20):8478-83
references.pmid: 17483484
references.citation: Microbiol Mol Biol Rev. 1999 Mar;63(1):174-229
references.pmid: 10066836
references.citation: J Biol Chem. 2001 Jun 22;276(25):22056-63
references.pmid: 11294844
references.citation: Genes Dev. 2001 Jul 1;15(13):1662-73
references.pmid: 11445541
references.citation: Mol Microbiol. 1999 Dec;34(5):902-14
references.pmid: 10594817
references.citation: Mol Microbiol. 1993 Apr;8(1):143-57
references.pmid: 8388529
references.citation: Adv Microb Physiol. 1988;29:233-302
references.pmid: 3289326
references.citation: Int J Syst Bacteriol. 1999 Apr;49 Pt 2:653-62
references.pmid: 10408878
references.citation: Mol Microbiol. 2002 Jan;43(1):1-14
references.pmid: 11849532
references.citation: J Bacteriol. 2007 Mar;189(6):2521-30
references.pmid: 17209021
references.citation: J Bacteriol. 1983 Nov;156(2):809-17
references.pmid: 6415040
references.citation: J Biol Chem. 2003 Mar 7;278(10):8420-8
references.pmid: 12464611
references.citation: Mol Microbiol. 1998 Mar;27(5):1077-87
references.pmid: 9535096
references.citation: Trends Microbiol. 2009 Jun;17(6):219-25
references.pmid: 19464183
references.citation: EMBO J. 2009 Apr 8;28(7):830-42
references.pmid: 19229300
references.citation: Mol Microbiol. 2009 Feb;71(4):1055-69
references.pmid: 19170884
references.citation: Gene. 1991 Jul 15;103(1):101-5
references.pmid: 1652539
references.citation: J Bacteriol. 2001 Jun;183(11):3506-14
references.pmid: 11344159
references.citation: Gene. 1989 Apr 15;77(1):61-8
references.pmid: 2744488
references.citation: Mol Microbiol. 2007 Aug;65(4):1078-91
references.pmid: 17640274
references.citation: J Immunol. 1987 Sep 15;139(6):2005-9
references.pmid: 3114382
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1584-9
references.pmid: 19168632
references.citation: Biochem Cell Biol. 1990 Jan;68(1):33-43
references.pmid: 2350496
references.citation: Nat Rev Microbiol. 2008 Apr;6(4):276-87
references.pmid: 18327271
references.citation: J Bacteriol. 2009 Jan;191(1):141-51
references.pmid: 18952789
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12318-23
references.pmid: 15302931
references.citation: J Clin Invest. 2005 Sep;115(9):2499-507
references.pmid: 16138192
references.citation: Biochim Biophys Acta. 1978 Mar 30;528(3):288-97
references.pmid: 638158
references.citation: J Bacteriol. 2002 Aug;184(15):4177-86
references.pmid: 12107135
references.citation: Eur J Biochem. 2000 Jun;267(12):3770-83
references.pmid: 10848996