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. 2008 Apr 10;13(2):212–229. doi: 10.2478/s11658-007-0048-4

Regulation of bacterial protease activity

Benedykt Władyka 1,✉, Katarzyna Pustelny 1
PMCID: PMC6275810  PMID: 18026858

Abstract

Proteases, also referred to as peptidases, are the enzymes that catalyse the hydrolysis of peptide bonds in polipeptides. A variety of biological functions and processes depend on their activity. Regardless of the organism’s complexity, peptidases are essential at every stage of life of every individual cell, since all protein molecules produced must be proteolytically processed and eventually recycled. Protease inhibitors play a crucial role in the required strict and multilevel control of the activity of proteases involved in processes conditioning both the physiological and pathophysiological functioning of an organism, as well as in host-pathogen interactions. This review describes the regulation of activity of bacterial proteases produced by dangerous human pathogens, focusing on the Staphylococcus genus.

Keywords: Protease, Protease inhibitor, Zymogen, Operon, Staphylococcus

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Glossary of Symbols

α2M

alpha2-macroglobulin

aa

amino acid

agr

accesory gene regulator

AprA

alkaline protease from Pseudomonas aeruginosa

aur

aureolysin gene

Clp

bacterial proteolytic system analogous to eukaryotic proteasome

ClpP

proteolytic core of the Clp

DegP

conserved heat shock protein

LasB

elastase from P. aeruginosa

RBS

ribosome binding site

sar

staphylococcal accessory regulator

scp

staphylococcal cysteine protease operon

SpeB

streptopain, cysteine protease form Streptococcus pyogenes

Spi

specific inhibitor of SpeB

spl

serine protease-like operon

ssp

staphylococcal serine protease operon

VVP

Vibro vulnificus protease

References

  • 1.Potempa J., Pike R.N. Bacterial peptidases. In: Russell W., Herwald H., editors. Concepts in Bacterial Virulence. Karger: Contrib Microbiol. Basel; 2005. pp. 132–180. [DOI] [PubMed] [Google Scholar]
  • 2.Yamaguchi T., Hayashi T., Takami H., Nakasone K., Ohnishi M., Nakayama K., Yamada S., Komatsuzawa H., Sugai M. Phage conversion of exfoliative toxin A production in Staphylococcus aureus. Mol. Microbiol. 2000;38:694–705. doi: 10.1046/j.1365-2958.2000.02169.x. [DOI] [PubMed] [Google Scholar]
  • 3.Yamaguchi T., Hayashi T., Takami H., Ohnishi M., Murata T., Nakayama K., Asakawa K., Ohara M., Komatsuzawa H., Sugai M. Complete nucleotide sequence of a Staphylococcus aureus exfoliative toxin B plasmid and identification of a novel ADP-ribosyltransferase, EDIN-C. Infect. Immun. 2001;69:7760–7771. doi: 10.1128/IAI.69.12.7760-7771.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Rice K., Peralta R., Bast D., De Azavedo J., McGavin M.J. Description of staphylococcus serine protease (ssp) operon in Staphylococcus aureus and nonpolar inactivation of sspA-encoded serine protease. Infect. Immun. 2001;69:159–169. doi: 10.1128/IAI.69.1.159-169.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Massimi I., Park E., Rice K., Muller-Esterl W., Sauder D., McGavin M.J. Identification of a novel maturation mechanism and restricted substrate specificity for the SspB cysteine protease of Staphylococcus aureus. J. Biol. Chem. 2002;277:41770–41777. doi: 10.1074/jbc.M207162200. [DOI] [PubMed] [Google Scholar]
  • 6.Rzychon M., Sabat A., Kosowska K., Potempa J., Dubin A. Staphostatins: an expanding new group of proteinase inhibitors with a unique specificity for the regulation of staphopains, Staphylococcus spp. cysteine proteinases. Mol. Microbiol. 2003;49:1051–1066. doi: 10.1046/j.1365-2958.2003.03613.x. [DOI] [PubMed] [Google Scholar]
  • 7.Dubin G., Krajewski M., Popowicz G., Stec-Niemczyk J., Bochtler M., Potempa J., Dubin A., Holak T.A. A novel class of cysteine protease inhibitors: solution structure of staphostatin A from Staphylococcus aureus. Biochemistry. 2003;42:13449–13456. doi: 10.1021/bi035310j. [DOI] [PubMed] [Google Scholar]
  • 8.Shaw L., Golonka E., Potempa J., Foster S.J. The role and regulation of the extracellular proteases of Staphylococcus aureus. Microbiology. 2004;150:217–228. doi: 10.1099/mic.0.26634-0. [DOI] [PubMed] [Google Scholar]
  • 9.Takeuchi S., Kinoshita T., Kaidoh T., Hashizume N. Purification and characterization of protease produced by Staphylococcus aureus isolated from a diseased chcken. Vet. Microbiol. 1999;67:195–202. doi: 10.1016/S0378-1135(99)00034-6. [DOI] [PubMed] [Google Scholar]
  • 10.Takeuchi S., Matsunaga K., Inubushi S., Higuchi H., Imaizumi K., Kaidoh T. Structural gene and strain specificity of a novel cysteine protease produced by Staphylococcus aureus isolated from a diseased chicken. Vet. Microbiol. 2002;89:201–210. doi: 10.1016/S0378-1135(02)00171-2. [DOI] [PubMed] [Google Scholar]
  • 11.Dubin G., Wladyka B., Stee-Niemczyk J., Chmiel D., Zdzalik M., Dubin A., Potempa J. The staphostatin family of cysteine protease inhibitors in Staphylococcus genus as an example of parallel evolution of protease and inhibitor specificity. Biol. Chem. 2007;388:227–235. doi: 10.1515/BC.2007.025. [DOI] [PubMed] [Google Scholar]
  • 12.Dubin G., Stec-Niemczyk J., Dylag T., Silbering J., Dubin A., Potempa J. Characterisation of a highly specific, endogenous inhibitor of cysteine protease from Staphylococcus epidermidis, a new member of the staphostatin family. Biol. Chem. 2004;385:543–546. doi: 10.1515/BC.2004.064. [DOI] [PubMed] [Google Scholar]
  • 13.Potempa J., Golonka E., Filipek R., Shaw L.N. Fighting an enemy within: cytoplasmic inhibitors of bacterial cysteine proteases. Mol. Microbiol. 2005;57:605–610. doi: 10.1111/j.1365-2958.2005.04714.x. [DOI] [PubMed] [Google Scholar]
  • 14.Reed S.B., Wesson C.A., Liou L.E., Trumble W.R., Schlievert P.M., Bohach G.A., Bayles K.W. Molecular characterization of a novel Staphylococcus aureus serine protease operon. Infect. Immun. 2001;69:1521–1527. doi: 10.1128/IAI.69.3.1521-1527.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Duong F., Lazdunski A., Cami B., Murgier M. Sequence of a cluster of genes controlling synthesis and secretion of alkaline proteinase in Pseudomonas aeruginosa: relationships to other secretory pathways. Gene. 1992;121:47–54. doi: 10.1016/0378-1119(92)90160-Q. [DOI] [PubMed] [Google Scholar]
  • 16.Kagawa T.F., O’Toole P.W., Cooney J.C. SpeB-Spi: a novel proteaseinhibitor pair from Streptococcus pyogenes. Mol. Microbiol. 2005;57:650–666. doi: 10.1111/j.1365-2958.2005.04708.x. [DOI] [PubMed] [Google Scholar]
  • 17.Rzychon M., Filipek R., Sabat A., Kosowska K., Potempa J., Dubin A., Bochtler M. Staphostatins resemble lipocalins, not cystatins in fold. Protein Sci. 2003;12:2252–2256. doi: 10.1110/ps.03247703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Recsei P., Kreiswirth B., O’Reilly M., Schlievert P., Gruss A., Novick R.P. Regulation of exoprotein gene expression in Staphylococcus aureus by agr. Mol. Gen. Genet. 1986;202:58–61. doi: 10.1007/BF00330517. [DOI] [PubMed] [Google Scholar]
  • 19.Bayer M.G., Heinrichs J.H., Cheung A.L. The molecular architecture of the sar locus in Staphylococcus aureus. J. Bacteriol. 1996;178:4563–4570. doi: 10.1128/jb.178.15.4563-4570.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Novick R.P., Projan S.J., Kornblum J., Ross H.F., Ji G., Kreiswirth B., Vandenesch F., Moghazeh S. The agr P2 operon: an autocatalytic sensory transduction system in Staphylococcus aureus. Mol. Gen. Genet. 1995;248:446–458. doi: 10.1007/BF02191645. [DOI] [PubMed] [Google Scholar]
  • 21.Ji G., Beavis R.C., Novick R.P. Cell density control of staphylococcal virulence mediated by an octapeptide pheromone. Proc. Natl. Acad. Sci. USA. 1995;92:12055–12059. doi: 10.1073/pnas.92.26.12055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Gambello M.J., Kaye S., Iglewski B.H. LasR of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxin A expression. Infect. Immun. 1993;61:1180–1184. doi: 10.1128/iai.61.4.1180-1184.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Passador L., Cook J.M., Gambello M.J., Rust L., Iglewski B.H. Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication. Science. 1993;260:1127–1130. doi: 10.1126/science.8493556. [DOI] [PubMed] [Google Scholar]
  • 24.Heinrichs J.H., Bayer M.G., Cheung A.L. Characterization of the sar locus and its interactions with agr in Staphylococcus aureus. J. Bacteriol. 1996;178:418–423. doi: 10.1128/jb.178.2.418-423.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Cheung A.L., Bayer M.G., Heinrichs J.H. sar genetic determinants necessary for transcription of RNAII and RNAIII in the agr locus of Staphylococcus aureus. J. Bacteriol. 1997;179:3963–3971. doi: 10.1128/jb.179.12.3963-3971.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Chien Y., Manna A.C., Projan S.J., Cheung A.L. SarA, a global regulator of virulence determinants in Staphylococcus aureus, binds to a conserved motif essential for sar-dependent gene regulation. J. Biol. Chem. 1999;274:37169–37176. doi: 10.1074/jbc.274.52.37169. [DOI] [PubMed] [Google Scholar]
  • 27.Chan P.F., Foster S.J. Role of SarA in virulence determinant production and environmental signal transduction in Staphylococcus aureus. J. Bacteriol. 1998;180:6232–6241. doi: 10.1128/jb.180.23.6232-6241.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.McNamara P.J., Milligan-Monroe K.C., Khalili S., Proctor R.A. Identification, cloning, and initial characterization of rot, a locus encoding a regulator of virulence factor expression in Staphylococcus aureus. J. Bacteriol. 2000;182:3197–3203. doi: 10.1128/JB.182.11.3197-3203.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Saïd-Salim B., Dunman P.M., McAleese F.M., Macapagal D., Murphy E., McNamara P.J., Arvidson S., Foster T.J., Projan S.J., Kreiswirth B.N. Global regulation of Staphylococcus aureus genes by Rot. J. Bacteriol. 2003;185:610–619. doi: 10.1128/JB.185.2.610-619.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Horsburgh M., Aish J., White I., Shaw L., Lithgow J., Foster S. SigmaB modulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus 8325-4. J. Bacteriol. 2002;184:5457–5467. doi: 10.1128/JB.184.19.5457-5467.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Shaw L.N., Golonka E., Szmyd G., Foster S.J., Travis J., Potempa J. Cytoplasmic control of premature activation of a secreted protease zymogen: deletion of staphostatin B (SspC) in Staphylococcus aureus 8325-4 yields a profound pleiotropic phenotype. J. Bacteriol. 2005;187:1751–1762. doi: 10.1128/JB.187.5.1751-1762.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Lowther W.T., Matthews B.W. Structure and function of the methionine aminopeptidases. Biochim. Biophys. Acta. 2000;1477:157–167. doi: 10.1016/s0167-4838(99)00271-x. [DOI] [PubMed] [Google Scholar]
  • 33.Tuteja R. Type I signal peptidase: an overview. Arch. Biochem. Biophys. 2005;441:107–111. doi: 10.1016/j.abb.2005.07.013. [DOI] [PubMed] [Google Scholar]
  • 34.Neurath H. The versatility of proteolytic enzymes. J. Cell Biochem. 1986;32:35–49. doi: 10.1002/jcb.240320105. [DOI] [PubMed] [Google Scholar]
  • 35.Vasantha N., Thompson L.D., Rhodes C., Banner C., Nagle J., Filpula D. Genes for alkaline protease and neutral protease from Bacillus amyloliquefaciens contain a large open reading frame between the regions coding for signal sequence and mature protein. J. Bacteriol. 1984;159:811–819. doi: 10.1128/jb.159.3.811-819.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Zhu X., Ohta Y., Jordan F., Inouye M. Pro-sequence of subtilisin can guide the refolding of denatured subtilisin in an intermolecular process. Nature. 1989;339:483–484. doi: 10.1038/339483a0. [DOI] [PubMed] [Google Scholar]
  • 37.Sabat A., Kosowska K., Poulsen K., Kasprowicz A., Sekowska A., van der Burg B., Travis J., Potempa J. Two allelic forms of the aureolysin gene (aur) within Staphylococcus aureus. Infect. Immun. 2000;68:973–976. doi: 10.1128/IAI.68.2.973-976.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Miyoshi S., Shinoda S. Microbal metalloproteases and pathogenesis. Microbes Infect. 2000;2:91–98. doi: 10.1016/S1286-4579(00)00280-X. [DOI] [PubMed] [Google Scholar]
  • 39.Carmona, C. and Gray, G.L. Nucleotide sequence of the serine protease gene of Staphylococcus aureus, strain V8. Nucleic Acids Res.15 (1987) 6757. [DOI] [PMC free article] [PubMed]
  • 40.Yoshikawa K., Tsuzuki H., Fujiwara T., Nakamura E., Iwamoto H., Matsumoto K., Shin M., Yoshida N., Teraoka H. Purification, characterization and gene cloning of a novel glutamic acid-specific endopeptidase from Staphylococcus aureus ATCC 12600. Biochim. Biophys. Acta. 1992;1121:221–228. doi: 10.1016/0167-4838(92)90358-k. [DOI] [PubMed] [Google Scholar]
  • 41.Beaudet R., Saheb S.A., Drapeau G.R. Structural heterogenicity of the protease isolated from several strains of Staphylococcus aureus. J. Biol. Chem. 1974;249:6468–6471. [PubMed] [Google Scholar]
  • 42.Drapeau G.R. Role of a metalloprotease in activation of the precursor of staphylococcal protease. J. Bacteriol. 1978;136:607–613. doi: 10.1128/jb.136.2.607-613.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Lindsay J., Foster S. Interactive regulatory pathways control virulence determinant production and stability in response to the environment in Staphylococcus aureus. Mol. Gen. Genet. 1999;262:323–331. doi: 10.1007/s004380051090. [DOI] [PubMed] [Google Scholar]
  • 44.Filipek R., Szczepanowski R., Sabat A., Potempa J., Bochtler M. Prostaphopain B structure: a comparison of proregion-mediated and staphostatin-mediated protease inhibition. Biochemistry. 2004;43:14306–14315. doi: 10.1021/bi048661m. [DOI] [PubMed] [Google Scholar]
  • 45.Popowicz G.M., Dubin G., Stec-Niemczyk J., Czarny A., Dubin A., Potempa J., Holak T.A. Functional and structural characterization of Spl proteases from Staphylococcus aureus. J. Mol. Biol. 2006;358:270–279. doi: 10.1016/j.jmb.2006.01.098. [DOI] [PubMed] [Google Scholar]
  • 46.Rasmussen M., Björck L. Proteolysis and its regulation at the surface of Streptococcus pyogenes. Mol. Microbiol. 2002;43:537–544. doi: 10.1046/j.1365-2958.2002.02766.x. [DOI] [PubMed] [Google Scholar]
  • 47.Kagawa T.F., Cooney J.C., Baker H.M., McSweeney S., Liu M., Gubba S., Musser J.M., Baker E.N. Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease. Proc. Natl. Acad. Sci. USA. 2000;97:2235–2240. doi: 10.1073/pnas.040549997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Doran J.D., Nomizu M., Takebe S., Ménard R., Griffith D., Ziomek E. Autocatalytic processing of the streptococcal cysteine protease zymogen: processing mechanism and characterization of the autoproteolytic cleavage sites. Eur. J. Biochem. 1999;263:145–151. doi: 10.1046/j.1432-1327.1999.00473.x. [DOI] [PubMed] [Google Scholar]
  • 49.Braun P., de Groot A., Bitter W., Tommassen J. Secretion of elastolytic enzymes and their propeptides by Pseudomonas aeruginosa. J. Bacteriol. 1998;173:3467–3469. doi: 10.1128/jb.180.13.3467-3469.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Miyoshi S., Wakae H., Tomochika K., Shinoda S. Functional domains of a zinc metalloprotease from Vibrio vulnificus. Infect. Immun. 1997;179:7606–7609. doi: 10.1128/jb.179.23.7606-7609.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Prokesová L., Porwit-Bobr Z., Baran K., Potempa J., Pospisil M., John C. Effect of metalloproteinase from Staphylococcus aureus on in vitro stimulation of human lymphocytes. Immun. Lett. 1991;27:225–230. doi: 10.1016/0165-2478(91)90156-5. [DOI] [PubMed] [Google Scholar]
  • 52.Potempa J., Watorek W., Travis J. The inactivation of human plasma a1-proteinase inhibitor by proteinases form Staphylococcus aureus. J. Biol. Chem. 1986;261:14330–14334. [PubMed] [Google Scholar]
  • 53.Potempa J., Fedak D., Dubin A., Mast A., Travis J. Proteolytic inactivation of α-1-antichymotrypsin. Sites of cleavage and generation of chemotactic activity. J. Biol. Chem. 1991;266:21482–21487. [PubMed] [Google Scholar]
  • 54.Amagai M., Matsuyoshi N., Wang Z.H., Andl C., Stanley J.R. Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein 1. Nature Med. 2000;6:1275–1277. doi: 10.1038/81385. [DOI] [PubMed] [Google Scholar]
  • 55.Arvidson, S. Extracellular enzymes. In: Gram-Positive Pathogens (Fischetti, V.A., Novick, R.P., Ferretti, J.J., Portnoy, D.A. and Rood, J.I. Eds.) Washington, D.C., USA, American Society for Microbiology, pp. 379–385.
  • 56.Potempa J., Dubin A., Korzus G., Travis J. Degradation of elastin by a cysteine proteinase from Staphylococcus aureus. J. Biol. Chem. 1988;263:2664–2667. [PubMed] [Google Scholar]
  • 57.Imamura T., Tanase S., Szmyd G., Kozik A., Travis J., Potempa J. Induction of vascular leakage through release of bradykinin and a novel kinin by cysteine proteinases from Staphylococcus aureus. J. Exp. Med. 2005;201:1669–1676. doi: 10.1084/jem.20042041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Rieneck K., Rennenberg J., Diamant M., Gutschik E., Bendtzen K. Molecular cloning and expression of novel Staphylococcus aureus antigen. Biochim. Biophys. Acta. 1997;44:128–132. doi: 10.1016/s0167-4781(96)00216-3. [DOI] [PubMed] [Google Scholar]
  • 59.Matsumoto K. Role of bacterial proteases in pseudomonal and serratial keratitis. Biol. Chem. 2004;385:1007–1016. doi: 10.1515/BC.2004.131. [DOI] [PubMed] [Google Scholar]
  • 60.Dubin G., Popowicz G., Krajewski M., Potempa J., Dubin A., Holak T.A. 1H, 15N and 13C NMR resonance assignments of staphostatin A, a specific Staphylococcus aureus cysteine proteinase inhibitor. J. Biomol. NMR. 2004;28:295–296. doi: 10.1023/B:JNMR.0000013681.37659.24. [DOI] [PubMed] [Google Scholar]
  • 61.Filipek R., Rzychon M., Oleksy A., Gruca M., Dubin A., Potempa J., Bochtler M. The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease. J. Biol. Chem. 2003;278:40959–40966. doi: 10.1074/jbc.M302926200. [DOI] [PubMed] [Google Scholar]
  • 62.Dubin G. Defense against own arms: staphylococcal cysteine proteases and their inhibitors. Acta Biochim. Polon. 2003;50:715–724. [PubMed] [Google Scholar]
  • 63.Wladyka B., Puzia K., Dubin A. Efficient co-expression of a recombinant staphopain A and its inhibitor staphostatin A in Escherichia coli. Biochem. J. 2005;385:181–187. doi: 10.1042/BJ20040958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Herwald H., Collin M., Muller-Esterl W., Björck L. Streptococcal cysteine proteinase releases kinins: a virulence mechanism. J. Exp. Med. 1996;184:665–673. doi: 10.1084/jem.184.2.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Schroeter J.P., Kolodziej S.J., Wagenknecht T., Bretaudiere J.P., Tapon-Bretaudiere J., Strickland D.K., Stoops J.K. Three-dimensional structures of the human alpha 2-macroglobulin-methylamine and chymotrypsin complexes. J. Struct. Biol. 1992;109:235–247. doi: 10.1016/1047-8477(92)90036-A. [DOI] [PubMed] [Google Scholar]
  • 66.Starkey P.M., Barrett A.J. Inhibition by α-macroglobulin and other serum proteins. Biochem. J. 1973;131:823–831. doi: 10.1042/bj1310823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Sottrup-Jensen L., Sand O., Kristensen L., Fey G.H. The α-macroglobulin bait region. Sequence diversity and localization of cleavage sites for proteinases in five mammalian a-macroglobulins. J. Biol. Chem. 1989;264:15781–15789. [PubMed] [Google Scholar]
  • 68.Maeda S., Molla T., Oda A., Katsuki T. Internalization of serratial protease into cells as an enzyme-inhibitor complex with α2-macroglobulin and regeneration of protease activity and cytotoxicity. J. Biol. Chem. 1987;262:10946–10950. [PubMed] [Google Scholar]
  • 69.Nyberg P., Rasmussen M., Björck L. αa2-macroglobulin-proteinase complexes protect Streptococcus pyogenes from killing by the antimicrobal peptide LL-37. J. Biol. Chem. 2004;279:52820–52823. doi: 10.1074/jbc.C400485200. [DOI] [PubMed] [Google Scholar]
  • 70.Giles, N.M., Watts, A.B., Giles, G.I., Fry, F.H., Littlechild, J.A. and Jacob, C. Metal and redox modulation of cysteine protein function. Chem. Biol.10 (200) 3677–1093. [DOI] [PubMed]
  • 71.Wasylewski Z., Stryjewski W., Wasniowska A., Potempa J., Baran K. Effect of calcium binding on conformational changes of staphylococcal metalloproteinase measured by means of intrinsic protein fluorescence. Biochim. Biophys. Acta. 1986;871:177–181. doi: 10.1016/0167-4838(86)90171-8. [DOI] [PubMed] [Google Scholar]
  • 72.Potempa J., Porwit-Bobr Z., Travis J. Stabilization vs. degradation of Staphylococcus aureus metalloproteinase. Biochim. Biophys. Acta. 1989;993:301–304. doi: 10.1016/0304-4165(89)90181-5. [DOI] [PubMed] [Google Scholar]
  • 73.Gottesman S. Regulation by proteolysis: developmental switches. Curr. Opin. Microbiol. 1999;2:142–147. doi: 10.1016/S1369-5274(99)80025-3. [DOI] [PubMed] [Google Scholar]
  • 74.Hoskins J.R., Singh A.K., Maurizi M.R., Wickner S. Protein binding and unfolding by the chaperone ClpA and degradation by the protease ClpAP. Proc. Natl. Acad. Sci. USA. 2000;97:8892–8897. doi: 10.1073/pnas.97.16.8892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Frees D., Qazi S.N., Hill P.J., Ingmer H. Alternative roles of ClpX and ClpP in Staphylococcus aureus stress tolerance and virulence. Mol. Microbiol. 2003;48:1565–1578. doi: 10.1046/j.1365-2958.2003.03524.x. [DOI] [PubMed] [Google Scholar]
  • 76.Frees D., Sørensen K., Ingmer H. Global virulence regulation in Staphylococcus aureus: pinpointing the roles of ClpP and ClpX in the sar/agr regulatory network. Infect. Immun. 2005;73:8100–8108. doi: 10.1128/IAI.73.12.8100-8108.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Butler S.M., Festa R.A., Pearce M.J., Darwin K.H. Selfcompartmentalized bacterial proteases and pathogenesis. Mol. Microbiol. 2006;60:553–562. doi: 10.1111/j.1365-2958.2006.05128.x. [DOI] [PubMed] [Google Scholar]
  • 78.Brötz-Oesterhelt H., Beyer D., Kroll H.P., Endermann R., Ladel C., Schroeder W., Hinzen B., Raddatz S., Paulsen H., Henninger K., Bandow J.E., Sahl H.G., Labischinski H. Disregulation of bacterial proteolytic machinery by a new class of antibiotics. Nat. Med. 2005;11:1082–1087. doi: 10.1038/nm1306. [DOI] [PubMed] [Google Scholar]
  • 79.Spiess C., Beil A., Ehrmann M. A temperature-dependent switch from chaperon to protease in widely conserved heat shock protein. Cell. 1999;97:339–347. doi: 10.1016/S0092-8674(00)80743-6. [DOI] [PubMed] [Google Scholar]
  • 80.Clausen T., Southan C., Ehrmann M. The HrtA family of proteases: implications for protein coposition and cell fate. Mol. Cell. 2002;10:443–455. doi: 10.1016/S1097-2765(02)00658-5. [DOI] [PubMed] [Google Scholar]

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