BMC Genomics | |
A network-based approach to identify substrate classes of bacterial glycosyltransferases | |
Kathleen Marchal4  Sarah Lebeer2  Jos Vanderleyden1  Joris Winderickx3  Hanne LP Tytgat2  Aminael Sánchez-Rodríguez5  | |
[1] Department of Microbial and Molecular Systems, KU Leuven, Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, box 2460, Leuven B-3001, Belgium;Department of Bioscience Engineering, University of Antwerp, Groenenborgerlaan 171, Antwerp B-2020, Belgium;Department of Biology, Functional Biology, KU Leuven, Kasteelpark Arenberg 31, box 2433, Leuven B-3001, Belgium;Department of Information Technology, Ghent University, IMinds, Gent 9052, Belgium;Departamento de Ciencias Naturales, Universidad Técnica Particular de Loja, San Cayetano Alto s/n Loja, Ecuador | |
关键词: Campylobacter jejuni; Lactobacillus rhamnosus GG; Glycosyltransferases; Bacterial glycosylation; Sequence-based prediction; Network-based prediction; | |
Others : 1217249 DOI : 10.1186/1471-2164-15-349 |
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received in 2013-12-25, accepted in 2014-04-16, 发布年份 2014 | |
【 摘 要 】
Background
Bacterial interactions with the environment- and/or host largely depend on the bacterial glycome. The specificities of a bacterial glycome are largely determined by glycosyltransferases (GTs), the enzymes involved in transferring sugar moieties from an activated donor to a specific substrate. Of these GTs their coding regions, but mainly also their substrate specificity are still largely unannotated as most sequence-based annotation flows suffer from the lack of characterized sequence motifs that can aid in the prediction of the substrate specificity.
Results
In this work, we developed an analysis flow that uses sequence-based strategies to predict novel GTs, but also exploits a network-based approach to infer the putative substrate classes of these predicted GTs. Our analysis flow was benchmarked with the well-documented GT-repertoire of Campylobacter jejuni NCTC 11168 and applied to the probiotic model Lactobacillus rhamnosus GG to expand our insights in the glycosylation potential of this bacterium. In L. rhamnosus GG we could predict 48 GTs of which eight were not previously reported. For at least 20 of these GTs a substrate relation was inferred.
Conclusions
We confirmed through experimental validation our prediction of WelI acting upstream of WelE in the biosynthesis of exopolysaccharides. We further hypothesize to have identified in L. rhamnosus GG the yet undiscovered genes involved in the biosynthesis of glucose-rich glycans and novel GTs involved in the glycosylation of proteins. Interestingly, we also predict GTs with well-known functions in peptidoglycan synthesis to also play a role in protein glycosylation.
【 授权许可】
2014 Sánchez-Rodríguez et al.; licensee BioMed Central Ltd.
【 预 览 】
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20150705193953871.pdf | 2779KB | download | |
Figure 5. | 82KB | Image | download |
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Figure 1. | 109KB | Image | download |
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【 参考文献 】
- [1]Kay E, Lesk VI, Tamaddoni-Nezhad A, Hitchen PG, Dell A, Sternberg MJ, Muggleton S, Wren BW: Systems analysis of bacterial glycomes. Biochem Soc Trans 2010, 38(5):1290-1293.
- [2]Upreti RK, Kumar M, Shankar V: Bacterial glycoproteins: functions, biosynthesis and applications. Proteomics 2003, 3(4):363-379.
- [3]Lairson LL, Henrissat B, Davies GJ, Withers SG: Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem 2008, 77:521-555.
- [4]Guerry P, Szymanski CM: Campylobacter sugars sticking out. Trends Microbiol 2008, 16(9):428-435.
- [5]Hug I, Feldman MF: Analogies and homologies in lipopolysaccharide and glycoprotein biosynthesis in bacteria. Glycobiology 2011, 21(2):138-151.
- [6]Typas A, Banzhaf M, Gross CA, Vollmer W: From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Microbiol 2012, 10(2):123-136.
- [7]Lerouge I, Vanderleyden J: O-antigen structural variation: mechanisms and possible roles in animal/plant-microbe interactions. FEMS Microbiol Rev 2002, 26(1):17-47.
- [8]Hansen SF, Bettler E, Rinnan A, Engelsen SB, Breton C: Exploring genomes for glycosyltransferases. Mol Biosyst 2010, 6(10):1773-1781.
- [9]Hansen SF, Bettler E, Wimmerova M, Imberty A, Lerouxel O, Breton C: Combination of several bioinformatics approaches for the identification of new putative glycosyltransferases in Arabidopsis. J Proteome Res 2009, 8(2):743-753.
- [10]Egelund J, Skjot M, Geshi N, Ulvskov P, Petersen BL: A complementary bioinformatics approach to identify potential plant cell wall glycosyltransferase-encoding genes. Plant Physiol 2004, 136(1):2609-2620.
- [11]Weerapana E, Imperiali B: Asparagine-linked protein glycosylation: from eukaryotic to prokaryotic systems. Glycobiology 2006, 16(6):91R-101R.
- [12]Faridmoayer A, Fentabil MA, Haurat MF, Yi W, Woodward R, Wang PG, Feldman MF: Extreme substrate promiscuity of the Neisseria oligosaccharyl transferase involved in protein O-glycosylation. J Biol Chem 2008, 283(50):34596-34604.
- [13]Wacker M, Feldman MF, Callewaert N, Kowarik M, Clarke BR, Pohl NL, Hernandez M, Vines ED, Valvano MA, Whitfield C, Aebi M: Substrate specificity of bacterial oligosaccharyltransferase suggests a common transfer mechanism for the bacterial and eukaryotic systems. Proc Natl Acad Sci U S A 2006, 103(18):7088-7093.
- [14]Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, Jensen LJ, von Mering C: The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 2011, 39(Database issue):D561-D568.
- [15]Claes IJ, Schoofs G, Regulski K, Courtin P, Chapot-Chartier MP, Rolain T, Hols P, von Ossowski I, Reunanen J, de Vos WM, Palva A, Vanderleyden J, De Keersmaecker SC, Lebeer S: Genetic and biochemical characterization of the cell wall hydrolase activity of the major secreted protein of Lactobacillus rhamnosus GG. PLoS One 2012, 7(2):e31588.
- [16]Ha S, Gross B, Walker S: E. Coli MurG: a paradigm for a superfamily of glycosyltransferases. Curr Drug Targets Infect Disord 2001, 1(2):201-213.
- [17]Di Guilmi AM, Dessen A, Dideberg O, Vernet T: The glycosyltransferase domain of penicillin-binding protein 2a from Streptococcus pneumoniae catalyzes the polymerization of murein glycan chains. J Bacteriol 2003, 185(15):4418-4423.
- [18]Maldonado-Barragan A, Caballero-Guerrero B, Lucena-Padros H, Ruiz-Barba JL: Genome sequence of Lactobacillus pentosus IG1, a strain isolated from Spanish-style green olive fermentations. J Bacteriol 2011, 193(19):5605.
- [19]Yoshida Y, Nakano Y, Yamashita Y, Koga T: Identification of a genetic locus essential for serotype b-specific antigen synthesis in Actinobacillus actinomycetemcomitans. Infect Immun 1998, 66(1):107-114.
- [20]Sun Y, Wang M, Wang Q, Cao B, He X, Li K, Feng L, Wang L: Genetic analysis of the Cronobacter sakazakii O4 to O7 O-antigen gene clusters and development of a PCR assay for identification of all C. sakazakii O serotypes. Appl Environ Microbiol 2012, 78(11):3966-3974.
- [21]Provencher C, LaPointe G, Sirois S, Van Calsteren MR, Roy D: Consensus-degenerate hybrid oligonucleotide primers for amplification of priming glycosyltransferase genes of the exopolysaccharide locus in strains of the Lactobacillus casei group. Appl Environ Microbiol 2003, 69(6):3299-3307.
- [22]Baiet B, Burel C, Saint-Jean B, Louvet R, Menu-Bouaouiche L, Kiefer-Meyer MC, Mathieu-Rivet E, Lefebvre T, Castel H, Carlier A, Cadoret JP, Lerouge P, Bardor M: N-glycans of Phaeodactylum tricornutum diatom and functional characterization of its N-acetylglucosaminyltransferase I enzyme. J Biol Chem 2011, 286(8):6152-6164.
- [23]Knauer R, Lehle L: The oligosaccharyltransferase complex from Saccharomyces cerevisiae. Isolation of the OST6 gene, its synthetic interaction with OST3, and analysis of the native complex. J Biol Chem 1999, 274(24):17249-17256.
- [24]Silberstein S, Collins PG, Kelleher DJ, Gilmore R: The essential OST2 gene encodes the 16-kD subunit of the yeast oligosaccharyltransferase, a highly conserved protein expressed in diverse eukaryotic organisms. J Cell Biol 1995, 131(2):371-383.
- [25]Campbell JA, Davies GJ, Bulone V, Henrissat B: A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem J 1997, 326(Pt 3):929-939.
- [26]Mengin-Lecreulx D, Texier L, Rousseau M, van Heijenoort J: The murG gene of Escherichia coli codes for the UDP-N-acetylglucosamine: N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase involved in the membrane steps of peptidoglycan synthesis. J Bacteriol 1991, 173(15):4625-4636.
- [27]Coutinho PM, Deleury E, Davies GJ, Henrissat B: An evolving hierarchical family classification for glycosyltransferases. J Mol Biol 2003, 328(2):307-317.
- [28]Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer EL, Eddy SR, Bateman A: The Pfam protein families database. Nucleic Acids Res 2010, 38(Database issue):D211-D222.
- [29]Finn RD, Clements J, Eddy SR: HMMER web server: interactive sequence similarity searching. Nucleic Acids Res 2011, 39(Web Server issue):W29-W37.
- [30]Lobley A, Sadowski MI, Jones DT: pGenTHREADER and pDomTHREADER: new methods for improved protein fold recognition and superfamily discrimination. Bioinformatics 2009, 25(14):1761-1767.
- [31]von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, Jouffre N, Huynen MA, Bork P: STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res 2005, 33(Database issue):D433-D437.
- [32]Storey JD, Tibshirani R: Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 2003, 100(16):9440-9445.
- [33]Nothaft H, Szymanski CM: Protein glycosylation in bacteria: sweeter than ever. Nat Rev Microbiol 2010, 8(11):765-778.
- [34]Szymanski CM, Logan SM, Linton D, Wren BW: Campylobacter–a tale of two protein glycosylation systems. Trends Microbiol 2003, 11(5):233-238.
- [35]Reeves PR, Hobbs M, Valvano MA, Skurnik M, Whitfield C, Coplin D, Kido N, Klena J, Maskell D, Raetz CR, Rick PD: Bacterial polysaccharide synthesis and gene nomenclature. Trends Microbiol 1996, 4(12):495-503.
- [36]Lebeer S, Claes IJ, Balog CI, Schoofs G, Verhoeven TL, Nys K, von Ossowski I, de Vos WM, Tytgat HL, Agostinis P, Palva A, Van Damme EJ, Deelder AM, De Keersmaecker SC, Wuhrer M, Vanderleyden J: The major secreted protein Msp1/p75 is O-glycosylated in Lactobacillus rhamnosus GG. Microb Cell Fact 2012, 11:15. BioMed Central Full Text
- [37]Lebeer S, Verhoeven TL, Francius G, Schoofs G, Lambrichts I, Dufrene Y, Vanderleyden J, De Keersmaecker SC: Identification of a gene cluster for the Biosynthesis of a long, Galactose-Rich Exopolysaccharide in Lactobacillus rhamnosus GG and functional analysis of the priming Glycosyltransferase. Appl Environ Microbiol 2009, 75(11):3554-3563.
- [38]Karlyshev AV, Ketley JM, Wren BW: The Campylobacter jejuni glycome. FEMS Microbiol Rev 2005, 29(2):377-390.
- [39]Linton D, Karlyshev AV, Wren BW: Deciphering Campylobacter jejuni cell surface interactions from the genome sequence. Curr Opin Microbiol 2001, 4(1):35-40.
- [40]Gundogdu O, Bentley SD, Holden MT, Parkhill J, Dorrell N, Wren BW: Re-annotation and re-analysis of the Campylobacter jejuni NCTC11168 genome sequence. BMC Genomics 2007, 8:162. BioMed Central Full Text
- [41]Lebeer S, Claes IJ, Verhoeven TL, Vanderleyden J, De Keersmaecker SC: Exopolysaccharides of Lactobacillus rhamnosus GG form a protective shield against innate immune factors in the intestine. Microb Biotechnol 2011, 4(3):368-374.
- [42]Kiel JA, Boels JM, Beldman G, Venema G: Glycogen in Bacillus subtilis: molecular characterization of an operon encoding enzymes involved in glycogen biosynthesis and degradation. Mol Microbiol 1994, 11(1):203-218.
- [43]Campbell RE, Mosimann SC, Tanner ME, Strynadka NC: The structure of UDP-N-acetylglucosamine 2-epimerase reveals homology to phosphoglycosyl transferases. Biochemistry 2000, 39(49):14993-15001.
- [44]Kankainen M, Paulin L, Tynkkynen S, von Ossowski I, Reunanen J, Partanen P, Satokari R, Vesterlund S, Hendrickx APA, Lebeer S, De Keersmaecker SCJ, Vanderleyden J, Hamalainen T, Laukkanen S, Salovuori N, Ritari J, Alatalo E, Korpela R, Mattila-Sandholm T, Lassig A, Hatakka K, Kinnunen KT, Karjalainen H, Saxelin M, Laakso K, Surakka A, Palva A, Salusjarvi T, Auvinen P, de Vos WM: Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human-mucus binding protein. Proc Natl Acad Sci USA 2009, 106(40):17193-17198.
- [45]Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, Henrissat B: The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res 2009, 37(Database issue):D233-D238.
- [46]Brew K, Tumbale P, Acharya KR: Family 6 glycosyltransferases in vertebrates and bacteria: inactivation and horizontal gene transfer may enhance mutualism between vertebrates and bacteria. J Biol Chem 2010, 285(48):37121-37127.
- [47]Mohammadi T, Karczmarek A, Crouvoisier M, Bouhss A, Mengin-Lecreulx D, den Blaauwen T: The essential peptidoglycan glycosyltransferase MurG forms a complex with proteins involved in lateral envelope growth as well as with proteins involved in cell division in Escherichia coli. Mol Microbiol 2007, 65(4):1106-1121.
- [48]Charbonneau ME, Cote JP, Haurat MF, Reiz B, Crepin S, Berthiaume F, Dozois CM, Feldman MF, Mourez M: A structural motif is the recognition site for a new family of bacterial protein O-glycosyltransferases. Mol Microbiol 2012, 83(5):894-907.
- [49]Grass S, Lichti CF, Townsend RR, Gross J, St Geme JW 3rd: The Haemophilus influenzae HMW1C protein is a glycosyltransferase that transfers hexose residues to asparagine sites in the HMW1 adhesin. PLoS Pathog 2010, 6(5):e1000919.
- [50]Wu R, Wu H: A molecular chaperone mediates a two-protein enzyme complex and glycosylation of serine-rich streptococcal adhesins. J Biol Chem 2011, 286(40):34923-34931.
- [51]Dell A, Galadari A, Sastre F, Hitchen P: Similarities and differences in the glycosylation mechanisms in prokaryotes and eukaryotes. Int J Microbiol 2010, 2010:148178.
- [52]Francius G, Lebeer S, Alsteens D, Wildling L, Gruber HJ, Hols P, Keersmaecker SD, Vanderleyden J, Dufrêne YF: Detection, localization, and conformational analysis of single polysaccharide molecules on live bacteria. ACS Nano 2008, 2(9):1921-1929.
- [53]Islam ST, Lam JS: Wzx flippase-mediated membrane translocation of sugar polymer precursors in bacteria. Environ Microbiol 2013, 15(4):1001-1015.
- [54]Lim WJ, Park SR, Kim MK, An CL, Yun HJ, Hong SY, Kim EJ, Shin EC, Lee SW, Lim YP, Yun HD: Cloning and characterization of the glycogen branching enzyme gene existing in tandem with the glycogen debranching enzyme from Pectobacterium chrysanthemi PY35. Biochem Biophys Res Commun 2003, 300(1):93-101.
- [55]Wilson WA, Roach PJ, Montero M, Baroja-Fernandez E, Munoz FJ, Eydallin G, Viale AM, Pozueta-Romero J: Regulation of glycogen metabolism in yeast and bacteria. FEMS Microbiol Rev 2010, 34(6):952-985.
- [56]Ballicora MA, Iglesias AA, Preiss J: ADP-glucose pyrophosphorylase, a regulatory enzyme for bacterial glycogen synthesis. Microbiol Mol Biol Rev 2003, 67(2):213-225.
- [57]van Heijenoort J: Formation of the glycan chains in the synthesis of bacterial peptidoglycan. Glycobiology 2001, 11(3):25R-36R.
- [58]Peregrin-Alvarez JM, Xiong X, Su C, Parkinson J: The modular organization of protein interactions in Escherichia coli. PLoS Comput Biol 2009, 5(10):e1000523.
- [59]Fletcher CM, Coyne MJ, Comstock LE: Theoretical and experimental characterization of the scope of protein O-glycosylation in Bacteroides fragilis. J Biol Chem 2011, 286(5):3219-3226.
- [60]Fredriksen L, Moen A, Adzhubei AA, Mathiesen G, Eijsink VG, Egge-Jacobsen W: Lactobacillus plantarum WCFS1 O-linked protein glycosylation: An extended spectrum of target proteins and modification sites detected by mass spectrometry. Glycobiology 2013, 23(12):1439-1451.
- [61]Fredriksen L, Mathiesen G, Moen A, Bron PA, Kleerebezem M, Eijsink VG, Egge-Jacobsen W: The major autolysin Acm2 from Lactobacillus plantarum undergoes cytoplasmic O-glycosylation. J Bacteriol 2012, 194(2):325-333.
- [62]Barinka C, Sacha P, Sklenar J, Man P, Bezouska K, Slusher BS, Konvalinka J: Identification of the N-glycosylation sites on glutamate carboxypeptidase II necessary for proteolytic activity. Protein Sci 2004, 13(6):1627-1635.
- [63]Commichau FM, Forchhammer K, Stulke J: Regulatory links between carbon and nitrogen metabolism. Curr Opin Microbiol 2006, 9(2):167-172.
- [64]Pimkin M, Miller CG, Blakesley L, Oleykowski CA, Kodali NS, Yeung AT: Characterization of a periplasmic S1-like nuclease coded by the Mesorhizobium loti symbiosis island. Biochem Biophys Res Commun 2006, 343(1):77-84.
- [65]Brechtel E, Matuschek M, Hellberg A, Egelseer EM, Schmid R, Bahl H: Cell wall of Thermoanaerobacterium thermosulfurigenes EM1: isolation of its components and attachment of the xylanase XynA. Arch Microbiol 1999, 171(3):159-165.
- [66]Huang L, Forsberg C, Thomas D: Purification and characterization of a chloride-stimulated cellobiosidase from Bacteroides succinogenes S85. J Bacteriol 1988, 170(7):2923-2932.
- [67]Olsen O, Thomsen KK: Improvement of bacterial β-glucanase thermostability by glycosylation. J Gen Microbiol 1991, 137(3):579-585.
- [68]Prachi T, Beaussart A, Andre G, Rolain T, Lebeer S, Vanderleyden J, Hols P, Dufrene YF: Towards a nanoscale view of lactic acid bacteria. Micron 2012, 43(12):1323-1330.
- [69]Zapun A, Noirclerc-Savoye M, Helassa N, Vernet T: Peptidoglycan assembly machines: the biochemical evidence. Microb Drug Resist 2012, 18(3):256-260.
- [70]Sauvage E, Kerff F, Terrak M, Ayala JA, Charlier P: The penicillin‒binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol Rev 2008, 32(2):234-258.
- [71]Rolain T, Bernard E, Beaussart A, Degand H, Courtin P, Egge-Jacobsen W, Bron PA, Morsomme P, Kleerebezem M, Chapot-Chartier M-P: O-glycosylation as a novel control mechanism of peptidoglycan hydrolase activity. J Biol Chem 2013, 288(31):22233-22247.