Lysostaphin

{{Infobox enzyme | name = Lysostaphin | image = 1QWY.png | EC_number = 3.4.24.75 | CAS_number = 9011-93-2 | GO_code = | width = 250 }} '''Lysostaphin''' ({{EC number|3.4.24.75}}, ''glycyl-glycine endopeptidase'') is a ''Staphylococcus simulans'' metalloendopeptidase ([http://www.rcsb.org/structure/4LXC crystal structure of lysostaphin]). It can function as a bacteriocin (antimicrobial) against ''Staphylococcus aureus''.<ref name="pmid12709327">{{cite journal | vauthors = Kokai-Kun JF, Walsh SM, Chanturiya T, Mond JJ | title = Lysostaphin cream eradicates Staphylococcus aureus nasal colonization in a cotton rat model | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 5 | pages = 1589–97 | date = May 2003 | pmid = 12709327 | pmc = 153340 | doi = 10.1128/AAC.47.5.1589-1597.2003 }}</ref>

Lysostaphin is a 27 kDa glycylglycine endopeptidase, an antibacterial enzyme which is capable of cleaving the crosslinking pentaglycine bridges found in the cell wall peptidoglycan of certain staphylococci. Lysostaphin was first isolated from a culture of ''Staphylococcus simulans'' by Schindler and Schuhardt in 1964.<ref>{{cite journal | vauthors = Schindler CA, Schuhardt VT | title =Lysostaphin: A New Bacteriolytic Agent for the ''Staphylococcus'' | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 51 | issue = 3 | pages = 414–21 | date = Mar 1964 | pmid = 14171453 | doi = 10.1073/pnas.51.3.414 | pmc=300087| bibcode =1964PNAS...51..414S | doi-access =free }}</ref> ''S. aureus'' cell walls contain high proportions of pentaglycine, making lysostaphin a highly effective agent against both actively growing and quiescent bacteria.<ref name = "Wu">{{cite journal | vauthors = Wu JA, Kusuma C, Mond JJ, Kokai-Kun JF | title = Lysostaphin disrupts Staphylococcus aureus and Staphylococcus epidermidis biofilms on artificial surfaces | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 11 | pages = 3407–14 | date = Nov 2003 | pmid = 14576095 | pmc = 253758 | doi = 10.1128/AAC.47.11.3407-3414.2003 }}</ref>

Staphylococcal infections of both ''Staphylococcus aureus'' and ''Staphylococcus epidermidis'' continue to be a major issue in clinical settings, particularly those with implantable devices. Staphylococci cause a significant percentage of device infections, and like many other pathogens, rather than living as free planktonic cells within the host they have the ability to form a multilayered community of sessile bacteria cells known as a biofilm on implantable devices. Once a staphylococcal biofilm has formed on an implanted medical device, it is difficult to disrupt due to its antibiotic resistance and protection against bacterial action.

Many studies have been previously published on lysostaphin since its isolation, both ''in vitro'' and ''in vivo''. Lysostaphin has been shown to eradicate susceptible ''S. aureus'' biofilms. It has also been reported to be effective in disrupting ''S. epidermidis'' biofilms ''in vitro'', albeit at higher concentrations of the enzyme.<ref name="Wu" /> Compared to commonly used antibiotics such as vancomycin, lysostaphin has been shown to demonstrate greater antibacterial activity ''in vitro''.<ref>{{cite journal | vauthors = Yang XY, Li CR, Lou RH, Wang YM, Zhang WX, Chen HZ, Huang QS, Han YX, Jiang JD, You XF | title = In vitro activity of recombinant lysostaphin against Staphylococcus aureus isolates from hospitals in Beijing, China | journal = Journal of Medical Microbiology | volume = 56 | issue = Pt 1 | pages = 71–6 | date = Jan 2007 | pmid = 17172520 | doi = 10.1099/jmm.0.46788-0 | doi-access = free }}</ref> The enzyme has demonstrated effectiveness against methicillin susceptible ''S. aureus'' (MSSA) and methicillin resistant ''S. aureus'' (MRSA) mediated keratitis ''in vivo'' in a rabbit model.<ref>{{cite journal | vauthors = Dajcs JJ, Hume EB, Moreau JM, Caballero AR, Cannon BM, O'Callaghan RJ | title = Lysostaphin treatment of methicillin-resistant Staphylococcus aureus keratitis in the rabbit | journal = Investigative Ophthalmology & Visual Science | volume = 41 | issue = 6 | pages = 1432–7 | date = May 2000 | pmid = 10798659 }}</ref> Additionally, it has been shown that lysostaphin combined with antimicrobials such as cefazolin, clarithromycin, doxycycline, levofloxacin, linezolid and quinuprisitin/dalfopristin has a synergistic effect for MSSA strains of the bacteria.<ref name=Aguinaga>{{cite journal | vauthors = Aguinaga A, Francés ML, Del Pozo JL, Alonso M, Serrera A, Lasa I, Leiva J | title = Lysostaphin and clarithromycin: a promising combination for the eradication of Staphylococcus aureus biofilms | journal = International Journal of Antimicrobial Agents | volume = 37 | issue = 6 | pages = 585–7 | date = Jun 2011 | pmid = 21497068 | doi = 10.1016/j.ijantimicag.2011.02.009 | hdl = 10261/49232 | hdl-access = free }}</ref> A study published by Belyansky et al. illustrated that a lysostaphin bound mesh demonstrated dramatic preservation results in a rat model.<ref>{{cite journal | vauthors = Belyansky I, Tsirline VB, Martin TR, Klima DA, Heath J, Lincourt AE, Satishkumar R, Vertegel A, Heniford BT | title = The addition of lysostaphin dramatically improves survival, protects porcine biomesh from infection, and improves graft tensile shear strength | journal = The Journal of Surgical Research | volume = 171 | issue = 2 | pages = 409–15 | date = Dec 2011 | pmid = 21696759 | doi = 10.1016/j.jss.2011.04.014 }}</ref>

Using lyostaphin to treat staphylococcal biofilm associated infections may prove to be preferable to using antibiotics as it may be possible to administer the enzyme at relatively low doses and disrupt a staphylococcal biofilm, therefore eliminating the need for surgical removal of the infected device.<ref name="Wu" />

== References == {{reflist}}

== External links == * The MEROPS online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=M23.004 M23.004] * {{MeshName|Lysostaphin}} * {{EC number|3.4.24.75}}

Category:EC 3.4.24 Category:Bacteriocins Category:Bactericides Category:Bacterial toxins Category:Antimicrobial peptides