Information de reference pour ce titreAccession Number: | 00005797-200708030-00014.
|
Author: | Kavanaugh, Jeffrey S.; Thoendel, Matthew; Horswill, Alexander R. *
|
Institution: | Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
|
Title: | |
Source: | Molecular Microbiology. 65(3):780-798, August 2007.
|
Abstract: | Summary: The Staphylococcus aureus Agr quorum-sensing system modulates the expression of extracellular virulence factors. The Agr system is controlled by an autoinducing peptide (AIP) molecule that is secreted during growth. In the AIP biosynthetic pathway, two proteolytic events are required to remove the leader and tail segments of AgrD, the peptide precursor of AIP. The only protein known to be involved in this pathway is AgrB, a membrane endopeptidase that removes the AgrD carboxy-tail. We designed a synthetic peptide substrate and developed an assay to detect peptidases that can remove the N-terminal leader of AIP. Several peptidase activities were detected in S. aureus extracts and these activities were present in both wild-type and agr mutant strains. Only one of these peptidases cleaved in the correct position and all properties of this enzyme were consistent with type I signal peptidase. Subsequent cloning and purification of the two known S. aureus signal peptidases, SpsA and SpsB, demonstrated that only SpsB catalysed this activity in vitro. To investigate the role of SpsB in AIP biosynthesis, SpsB peptide inhibitors were designed and characterized. The most effective inhibitor blocked SpsB activity in vitro and showed antibacterial activity against S. aureus. Importantly, the inhibitor reduced expression of an Agr-dependent reporter and inhibited AIP production in S. aureus, indicating a role for SpsB in quorum sensing.
Copyright (C) 2007 Blackwell Publishing Ltd.
|
References: | Allsop, A., Brooks, G., Edwards, P.D., Kaura, A.C., and Southgate, R. (1996) Inhibitors of bacterial signal peptidase: a series of 6-(substituted oxyethyl)penems. J Antibiot (Tokyo) 49: 921-928.
Arvidson, S. (1973) Studies on extracellular proteolytic enzymes from Staphylococcus aureus. II. Isolation and characterization of an EDTA-sensitive protease. Biochim Biophys Acta 302: 149-157.
Autret, N., Raynaud, C., Dubail, I., Berche, P., and Charbit, A. (2003) Identification of the agr locus of Listeria monocytogenes: role in bacterial virulence. Infect Immun 71: 4463-4471.
Bae, T., and Schneewind, O. (2006) Allelic replacement in Staphylococcus aureus with inducible counter-selection. Plasmid 55: 58-63.
Barkocy-Gallagher, G.A., and Bassford, P.J., Jr (1992) Synthesis of precursor maltose-binding protein with proline in the +1 position of the cleavage site interferes with the activity of Escherichia coli signal peptidase I in vivo. J Biol Chem 267: 1231-1238.
Bartolome, B., Jubete, Y., Martinez, E., and de la Cruz, F. (1991) Construction and properties of a family of pACYC184-derived cloning vectors compatible with pBR322 and its derivatives. Gene 102: 75-78.
Bourgogne, A., Hilsenbeck, S.G., Dunny, G.M., and Murray, B.E. (2006) Comparison of OG1RF and an isogenic fsrB deletion mutant by transcriptional analysis: the Fsr system of Enterococcus faecalis is more than the activator of gelatinase and serine protease. J Bacteriol 188: 2875-2884.
Bruton, G., Huxley, A., O'Hanlon, P., Orlek, B., Eggleston, D., Humphries, J., et al. (2003) Lipopeptide substrates for SpsB, the Staphylococcus aureus type I signal peptidase: design, conformation and conversion to alpha-ketoamide inhibitors. Eur J Med Chem 38: 351-356.
Chan, W.C., Coyle, B.J., and Williams, P. (2004) Virulence regulation and quorum sensing in staphylococcal infections: competitive AgrC antagonists as quorum sensing inhibitors. J Med Chem 47: 4633-4641.
Chandler, J.R., and Dunny, G.M. (2004) Enterococcal peptide sex pheromones: synthesis and control of biological activity. Peptides 25: 1377-1388.
Cregg, K.M., Wilding, I., and Black, M.T. (1996) Molecular cloning and expression of the spsB gene encoding an essential type I signal peptidase from Staphylococcus aureus. J Bacteriol 178: 5712-5718.
Dassanayake, R.P., Caceres, N.E., Sarath, G., and Duhamel, G.E. (2004) Biochemical properties of membrane-associated proteases of Brachyspira pilosicoli isolated from humans with intestinal disorders. J Med Microbiol 53: 319-323.
Drapeau, G.R. (1978) Role of metalloprotease in activation of the precursor of staphylococcal protease. J Bacteriol 136: 607-613.
Dubin, G. (2002) Extracellular proteases of Staphylococcus spp. Biol Chem 383: 1075-1086.
Dubin, G. (2003) Defense against own arms: staphylococcal cysteine proteases and their inhibitors. Acta Biochim Pol 50: 715-724.
Fleming, V., Feil, E., Sewell, A.K., Day, N., Buckling, A., and Massey, R.C. (2006) Agr interference between clinical Staphylococcus aureus strains in an insect model of virulence. J Bacteriol 188: 7686-7688.
Forsyth, R.A., Haselbeck, R.J., Ohlsen, K.L., Yamamoto, R.T., Xu, H., Trawick, J.D., et al. (2002) A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol 43: 1387-1400.
Garvis, S., Mei, J.M., Ruiz-Albert, J., and Holden, D.W. (2002) Staphylococcus aureus svrA: a gene required for virulence and expression of the agr locus. Microbiology 148: 3235-3243.
Geisinger, E., Adhikari, R.P., Jin, R., Ross, H.F., and Novick, R.P. (2006) Inhibition of rot translation by RNAIII, a key feature of agr function. Mol Microbiol 61: 1038-1048.
Heussen, C., and Dowdle, E.B. (1980) Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem 102: 196-202.
Horsburgh, M.J., Aish, J.L., White, I.J., Shaw, L., Lithgow, J.K., and Foster, S.J. (2002) sigmaB modulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus 8325-4. J Bacteriol 184: 5457-5467.
Inoue, H., Nojima, H., and Okayama, H. (1990) High efficiency transformation of Escherichia coli with plasmids. Gene 96: 23-28.
Janzon, L., Lofdahl, S., and Arvidson, S. (1989) Identification and nucleotide sequence of the delta-lysin gene, hld, adjacent to the accessory gene regulator (agr) of Staphylococcus aureus. Mol Gen Genet 219: 480-485.
Jarraud, S., Lyon, G.J., Figueiredo, A.M., Gerard, L., Vandenesch, F., Etienne, J., et al. (2000) Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus. J Bacteriol 182: 6517-6522.
Jarraud, S., Mougel, C., Thioulouse, J., Lina, G., Meugnier, H., Forey, F., et al. (2002) Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun 70: 631-641.
Ji, G., Beavis, R., and Novick, R.P. (1997) Bacterial interference caused by autoinducing peptide variants. Science 276: 2027-2030.
Kalkum, M., Lyon, G.J., and Chait, B.T. (2003) Detection of secreted peptides by using hypothesis-driven multistage mass spectrometry. Proc Natl Acad Sci USA 100: 2795-2800.
Koenig, R.L., Ray, J.L., Maleki, S.J., Smeltzer, M.S., and Hurlburt, B.K. (2004) Staphylococcus aureus AgrA binding to the RNAIII-agr regulatory region. J Bacteriol 186: 7549-7555.
Kong, K.F., Vuong, C., and Otto, M. (2006) Staphylococcus quorum sensing in biofilm formation and infection. Int J Med Microbiol 296: 133-139.
Kulanthaivel, P., Kreuzman, A.J., Strege, M.A., Belvo, M.D., Smitka, T.A., Clemens, M., et al. (2004) Novel lipoglycopeptides as inhibitors of bacterial signal peptidase I. J Biol Chem 279: 36250-36258.
Lazazzera, B.A. (2001) The intracellular function of extracellular signaling peptides. Peptides 22: 1519-1527.
Lazazzera, B.A., Solomon, J.M., and Grossman, A.D. (1997) An exported peptide functions intracellularly to contribute to cell density signaling in B. subtilis. Cell 89: 917-925.
Lina, G., Jarraud, S., Ji, G., Greenland, T., Pedraza, A., Etienne, J., et al. (1998) Transmembrane topology and histidine protein kinase activity of AgrC, the agr signal receptor in Staphylococcus aureus. Mol Microbiol 28: 655-662.
Lowy, F.D. (1998) Staphylococcus aureus infections. N Engl J Med 339: 520-532.
Lyon, G.J., and Novick, R.P. (2004) Peptide signaling in Staphylococcus aureus and other Gram-positive bacteria. Peptides 25: 1389-1403.
Muir, T.W. (2003) Turning virulence on and off in staphylococci. J Pept Sci 9: 612-619.
Nakayama, J., Cao, Y., Horii, T., Sakuda, S., Akkermans, A.D., de Vos, W.M., and Nagasawa, H. (2001) Gelatinase biosynthesis-activating pheromone: a peptide lactone that mediates a quorum sensing in Enterococcus faecalis. Mol Microbiol 41: 145-154.
Novick, R.P. (1991) Genetic systems in staphylococci. Methods Enzymol 204: 587-636.
Novick, R.P. (2003) Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48: 1429-1449.
Novick, R.P., Ross, H.F., Projan, S.J., Kornblum, J., Kreiswirth, B., and Moghazeh, S. (1993a) Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J 12: 3967-3975.
Novick, R.P., Ross, H.F., Projan, S.J., Kornblum, J., Kreiswirth, B., and Moghazeh, S. (1993b) Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J 12: 3967-3975.
Paetzel, M., Karla, A., Strynadka, N.C., and Dalbey, R.E. (2002) Signal peptidases. Chem Rev 102: 4549-4580.
Perego, M., and Brannigan, J.A. (2001) Pentapeptide regulation of aspartyl-phosphate phosphatases. Peptides 22: 1541-1547.
Qiu, R., Pei, W., Zhang, L., Lin, J., and Ji, G. (2005) Identification of the putative staphylococcal AgrB catalytic residues involving the proteolytic cleavage of AgrD to generate autoinducing peptide. J Biol Chem 280: 16695-16704.
van Roosmalen, M.L., Jongbloed, J.D., de Jonf, A., van Eerden, J., Venema, G., Bron, S., and van Dijl, J.M. (2001) Detergent-independent in vitro activity of a truncated Bacillus signal peptidase. Microbiology 147: 909-917.
van Roosmalen, M.L., Geukens, N., Jongbloed, J.D., Tjalsma, H., Dubois, J.Y., Bron, S., et al. (2004) Type I signal peptidases of Gram-positive bacteria. Biochim Biophys Acta 1694: 279-297.
Saenz, H.L., Augsburger, V., Vuong, C., Jack, R.W., Gotz, F., and Otto, M. (2000) Inducible expression and cellular location of AgrB, a protein involved in the maturation of the staphylococcal quorum-sensing pheromone. Arch Microbiol 174: 452-455.
Shanks, R.M., Donegan, N.P., Graber, M.L., Buckingham, S.E., Zegans, M.E., Cheung, A.L., and O'Toole, G.A. (2005) Heparin stimulates Staphylococcus aureus biofilm formation. Infect Immun 73: 4596-4606.
Shaw, L., Golonka, E., Potempa, J., and Foster, S.J. (2004) The role and regulation of the extracellular proteases of Staphylococcus aureus. Microbiology 150: 217-228.
Sibbald, M.J., Ziebandt, A.K., Engelmann, S., Hecker, M., de Jong, A., Harmsen, H.J., et al. (2006) Mapping the pathways to staphylococcal pathogenesis by comparative secretomics. Microbiol Mol Biol Rev 70: 755-788.
Slamti, L., and Lereclus, D. (2002) A cell-cell signaling peptide activates the PlcR virulence regulon in bacteria of the Bacillus cereus group. EMBO J 21: 4550-4559.
Stephenson, S., Mueller, C., Jiang, M., and Perego, M. (2003) Molecular analysis of Phr peptide processing in Bacillus subtilis. J Bacteriol 185: 4861-4871.
Sturme, M.H., Nakayama, J., Molenaar, D., Murakami, Y., Kunugi, R., Fujii, T., et al. (2005) An agr-like two-component regulatory system in Lactobacillus plantarum is involved in production of a novel cyclic peptide and regulation of adherence. J Bacteriol 187: 5224-5235.
Wang, P.Z., and Novick, R.P. (1987) Nucleotide sequence and expression of the beta-lactamase gene from Staphylococcus aureus plasmid pI258 in Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. J Bacteriol 169: 1763-1766.
Wright, J.S., 3rd, Jin, R., and Novick, R.P. (2005) Transient interference with staphylococcal quorum sensing blocks abscess formation. Proc Natl Acad Sci USA 102: 1691-1696.
Yarwood, J.M., Bartels, D.J., Volper, E.M., and Greenberg, E.P. (2004) Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol 186: 1838-1850.
Zhang, L., Gray, L., Novick, R.P., and Ji, G. (2002) Transmembrane topology of AgrB, the protein involved in the post-translational modification of AgrD in Staphylococcus aureus. J Biol Chem 277: 34736-34742.
Zhang, L., Lin, J., and Ji, G. (2004) Membrane anchoring of the AgrD N-terminal amphipathic region is required for its processing to produce a quorum-sensing pheromone in Staphylococcus aureus. J Biol Chem 279: 19448-19456.
Zhong, W., and Benkovic, S.J. (1998) Development of an internally quenched fluorescent substrate for Escherichia coli leader peptidase. Anal Biochem 255: 66-73.
|
Language: | English.
|
Document Type: | Research Article.
|
Journal Subset: | Life Sciences.
|
ISSN: | 0950-382X
|
NLM Journal Code: | mom, 8712028
|
Annotation(s) | |
|
|