Staphopain A
Identifiers
EC no.3.4.22.48
CAS no.347841-89-8
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Search
PMCarticles
PubMedarticles
NCBIproteins

Staphopain A (EC 3.4.22.48, ScpA, ScpAaur, staphylopain A, staphylococcal cysteine proteinase) is a secreted cysteine protease produced by Staphylococcus aureus. It was first identified in the S. aureus V8 strain as a papain-like cysteine protease. The protease distinguishes itself from the other major proteases of S. aureus in its very broad specificity and its ability to degrade elastin.[1][2]

Genetics

Staphopain A expressed from the gene scpA within the scp operon. The operon also contains the gene scpB for staphostatin A (specific inhibitor of staphopain A), downstream of scpA.[3][4]

Staphopain A is largely co-expressed with the other three major proteases of S. aureus: aureolysin, glutamyl endopeptidase, and staphopain B. The transcription of scp occurs via a promoter controlled by "housekeeping" sigma factor σA and up-regulated by accessory gene regulator agr. It is at also repressed by staphylococcal accessory regulator sarA and by alternative sigma factor σB (a stress response modulator of Gram-positive bacteria). ssp expression is highly expressed in post-exponential growth phase.[4] A more complex network of modulators and of environmental conditions affecting ssp expression have been suggested, however. Up-regulation of aureolysin during phagocytosis have also been observed.[5][6]

The scpA gene has a high prevalence in the genome of both commensal- and pathogenic-type S. aureus strains.[7]

Activation & inhibition

Staphopain A is expressed as an inactive zymogen. In contrast to the other proteases, however, it appears to undergo rapid autocatalytic activation. It is thus also independent of the activation cascade of the three other proteases.[4][8]

S. aureus expresses the intracellular inhibitor staphostatin A, specific against staphopain A. As the activation of staphopain A could occur before it has been secreted by the bacteria, the staphostatin acts as prevention against harmful intracellular activity of the protease.[3][8][9]

Function

Staphopain A is elastinolytic to a degree fairly equal to that of neutrophil elastase, and has a very broad specificity proteolysis.[1][2][10]

Staphopain A is inhibited by phosphorylated cystatin α and α2-macroglobulin.[1][2]

Staphopain A can cleave and lower the activity α1-antitrypsin,[1][2] and inactivate several complement system components.[11]

Biological significance

Staphopain A was shown to inhibit activation of the complement system activation by cleaving components that are part of all three pathways (the classical, alternative, and lectin pathways) of activation. It shows a duplex role in affecting chemotaxis; while inactivating neutrophil CXCR2 receptor, generates an active C5a fragment of C5 (although inactivating C5b).[11][12] However, it has yet to prove any significant impact on the outcome of infection. Inhibition of staphopain A by phosphorylated cystatin α did prevent colony formation in skin tissue, but the effect could also be attributed to staphopain B. Mutation of scpA did not show any impact on the outcome of a skin abscess nor a septic arthritis model.[4][13][14][15] Overlapping activity with the other proteases, plus the complexity of virulence determinants and the infection site environment makes it difficult to determine the impact of the protease in pathogenesis.[1][2]

The elastinolytic properties of the protease could assist in spread of bacteria and also symptomatically to connective tissue destruction.[1][2][10]

Staphopain A participates in S. aureus self-regulatory events, by altering the phenotype of the bacteria via cleavage of surface proteins and by preventing biofilm formation.[1][16]

References

  1. 1 2 3 4 5 6 7 Kantyka T, Shaw LN, Potempa J (January 2013). Rawlings ND, Salvesen G (eds.). Handbook of Proteolytic Enzymes. Academic Press. pp. 2150–2157. doi:10.1016/b978-0-12-382219-2.00483-x. ISBN 9780123822192.
  2. 1 2 3 4 5 6 Dubin G (July 2002). "Extracellular proteases of Staphylococcus spp". Biological Chemistry. 383 (7–8): 1075–86. doi:10.1515/BC.2002.116. PMID 12437090.
  3. 1 2 Filipek R, Rzychon M, Oleksy A, Gruca M, Dubin A, Potempa J, Bochtler M (October 2003). "The Staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease". The Journal of Biological Chemistry. 278 (42): 40959–66. doi:10.1074/jbc.M302926200. PMID 12874290.
  4. 1 2 3 4 Shaw L, Golonka E, Potempa J, Foster SJ (January 2004). "The role and regulation of the extracellular proteases of Staphylococcus aureus". Microbiology. 150 (Pt 1): 217–28. doi:10.1099/mic.0.26634-0. PMID 14702415.
  5. ↑ Oscarsson J, Tegmark-Wisell K, Arvidson S (October 2006). "Coordinated and differential control of aureolysin (aur) and serine protease (sspA) transcription in Staphylococcus aureus by sarA, rot and agr (RNAIII)". International Journal of Medical Microbiology. 296 (6): 365–80. doi:10.1016/j.ijmm.2006.02.019. PMID 16782403.
  6. ↑ Lindsay JA, Foster SJ (September 1999). "Interactive regulatory pathways control virulence determinant production and stability in response to environmental conditions in Staphylococcus aureus". Molecular & General Genetics. 262 (2): 323–31. doi:10.1007/s004380051090. PMID 10517329.
  7. ↑ Zdzalik M, Karim AY, Wolski K, Buda P, Wojcik K, Brueggemann S, Wojciechowski P, Eick S, Calander AM, Jonsson IM, Kubica M, Polakowska K, Miedzobrodzki J, Wladyka B, Potempa J, Dubin G (November 2012). "Prevalence of genes encoding extracellular proteases in Staphylococcus aureus - important targets triggering immune response in vivo". FEMS Immunology and Medical Microbiology. 66 (2): 220–9. doi:10.1111/j.1574-695X.2012.01005.x. PMID 22762789.
  8. 1 2 Nickerson N, Ip J, Passos DT, McGavin MJ (January 2010). "Comparison of Staphopain A (ScpA) and B (SspB) precursor activation mechanisms reveals unique secretion kinetics of proSspB (Staphopain B), and a different interaction with its cognate Staphostatin, SspC". Molecular Microbiology. 75 (1): 161–77. doi:10.1111/j.1365-2958.2009.06974.x. PMID 19943908.
  9. ↑ Dubin G (January 2003). "Defense against own arms: staphylococcal cysteine proteases and their inhibitors" (PDF). Acta Biochimica Polonica. 50 (3): 715–24. PMID 14515151.
  10. 1 2 Potempa J, Dubin A, Korzus G, Travis J (February 1988). "Degradation of elastin by a cysteine proteinase from Staphylococcus aureus". The Journal of Biological Chemistry. 263 (6): 2664–7. PMID 3422637.
  11. 1 2 Jusko M, Potempa J, Kantyka T, Bielecka E, Miller HK, Kalinska M, Dubin G, Garred P, Shaw LN, Blom AM (January 2014). "Staphylococcal proteases aid in evasion of the human complement system". Journal of Innate Immunity. 6 (1): 31–46. doi:10.1159/000351458. PMC 3972074. PMID 23838186.
  12. ↑ Laarman AJ, Mijnheer G, Mootz JM, van Rooijen WJ, Ruyken M, Malone CL, Heezius EC, Ward R, Milligan G, van Strijp JA, de Haas CJ, Horswill AR, van Kessel KP, Rooijakkers SH (August 2012). "Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation and chemotaxis". The EMBO Journal. 31 (17): 3607–19. doi:10.1038/emboj.2012.212. PMC 3433787. PMID 22850671.
  13. ↑ Takahashi M, Tezuka T, Korant B, Katunuma N (January 1999). "Inhibition of cysteine protease and growth of Staphylococcus aureus V8 and poliovirus by phosphorylated cystatin alpha conjugate of skin". BioFactors. 10 (4): 339–45. doi:10.1002/biof.5520100404. PMID 10619701.
  14. ↑ Kasprzykowski F, Schalén C, Kasprzykowska R, Jastrzebska B, Grubb A (July 2000). "Synthesis and antibacterial properties of peptidyl derivatives and cyclopeptides structurally based upon the inhibitory centre of human cystatin C. Dissociation of antiproteolytic and antibacterial effects". APMIS. 108 (7–8): 473–81. doi:10.1034/j.1600-0463.2000.d01-85.x. PMID 11167542.
  15. ↑ Calander AM, Jonsson IM, Kanth A, Arvidsson S, Shaw L, Foster SJ, Tarkowski A (February 2004). "Impact of staphylococcal protease expression on the outcome of infectious arthritis". Microbes and Infection. 6 (2): 202–6. doi:10.1016/j.micinf.2003.10.015. PMID 14998519.
  16. ↑ Mootz JM, Malone CL, Shaw LN, Horswill AR (September 2013). "Staphopains modulate Staphylococcus aureus biofilm integrity". Infection and Immunity. 81 (9): 3227–38. doi:10.1128/IAI.00377-13. PMC 3754231. PMID 23798534.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.