Staphopain A (Staphylococcus aureus) explained

Staphopain A
Ec Number:3.4.22.48
Cas Number:347841-89-8
Glutamyl endopeptidase

Staphopain A (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. 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.[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.[9]

Function

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

Staphopain A is inhibited by phosphorylated cystatin α and α2-macroglobulin.

Staphopain A can cleave and lower the activity α1-antitrypsin, 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.[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.

The elastinolytic properties of the protease could assist in spread of bacteria and also symptomatically to connective tissue destruction.

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.[16]

Notes and References

  1. Book: Handbook of Proteolytic Enzymes . Kantyka . Tomasz . Shaw . Lindsey N. . Potempa . Jan . vanc . January 2013 . Academic Press. 9780123822192. Rawlings. Neil D.. 2150–2157. 10.1016/b978-0-12-382219-2.00483-x. Salvesen. Guy.
  2. Dubin G . Extracellular proteases of Staphylococcus spp . Biological Chemistry . 383 . 7–8 . 1075–86 . July 2002 . 12437090 . 10.1515/BC.2002.116 .
  3. 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 . The Journal of Biological Chemistry . 278 . 42 . 40959–66 . October 2003 . 12874290 . 10.1074/jbc.M302926200 . free .
  4. Shaw L, Golonka E, Potempa J, Foster SJ . The role and regulation of the extracellular proteases of Staphylococcus aureus . Microbiology . 150 . Pt 1 . 217–28 . January 2004 . 14702415 . 10.1099/mic.0.26634-0 . free .
  5. Oscarsson J, Tegmark-Wisell K, Arvidson S . 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 . October 2006 . 16782403 . 10.1016/j.ijmm.2006.02.019 .
  6. Lindsay JA, Foster SJ . Interactive regulatory pathways control virulence determinant production and stability in response to environmental conditions in Staphylococcus aureus . Molecular & General Genetics . 262 . 2 . 323–31 . September 1999 . 10517329 . 10.1007/s004380051090.
  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 . 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 . November 2012 . 22762789 . 10.1111/j.1574-695X.2012.01005.x . free .
  8. Nickerson N, Ip J, Passos DT, McGavin MJ . 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 . January 2010 . 19943908 . 10.1111/j.1365-2958.2009.06974.x . free .
  9. Dubin G . Defense against own arms: staphylococcal cysteine proteases and their inhibitors . Acta Biochimica Polonica . 50 . 3 . 715–24 . January 2003 . 10.18388/abp.2003_3662 . 14515151 .
  10. Potempa J, Dubin A, Korzus G, Travis J . Degradation of elastin by a cysteine proteinase from Staphylococcus aureus . The Journal of Biological Chemistry . 263 . 6 . 2664–7 . February 1988 . 10.1016/S0021-9258(18)69118-5 . free . 3422637 .
  11. Jusko M, Potempa J, Kantyka T, Bielecka E, Miller HK, Kalinska M, Dubin G, Garred P, Shaw LN, Blom AM . Staphylococcal proteases aid in evasion of the human complement system . Journal of Innate Immunity . 6 . 1 . 31–46 . January 2014 . 23838186 . 3972074 . 10.1159/000351458 .
  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 . Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation and chemotaxis . The EMBO Journal . 31 . 17 . 3607–19 . August 2012 . 22850671 . 3433787 . 10.1038/emboj.2012.212 .
  13. Takahashi M, Tezuka T, Korant B, Katunuma N . Inhibition of cysteine protease and growth of Staphylococcus aureus V8 and poliovirus by phosphorylated cystatin alpha conjugate of skin . BioFactors . 10 . 4 . 339–45 . January 1999 . 10619701 . 10.1002/biof.5520100404.
  14. Kasprzykowski F, Schalén C, Kasprzykowska R, Jastrzebska B, Grubb A . 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 . . 108 . 7–8 . 473–81 . July 2000 . 11167542 . 10.1034/j.1600-0463.2000.d01-85.x. 2024-04-25 .
  15. Calander AM, Jonsson IM, Kanth A, Arvidsson S, Shaw L, Foster SJ, Tarkowski A . Impact of staphylococcal protease expression on the outcome of infectious arthritis . Microbes and Infection . 6 . 2 . 202–6 . February 2004 . 14998519 . 10.1016/j.micinf.2003.10.015 .
  16. Mootz JM, Malone CL, Shaw LN, Horswill AR . Staphopains modulate Staphylococcus aureus biofilm integrity . Infection and Immunity . 81 . 9 . 3227–38 . September 2013 . 23798534 . 3754231 . 10.1128/IAI.00377-13 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Staphopain A (Staphylococcus aureus)".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.