Lysostaphin

Lysostaphin (EC 3.4.24.75, glycyl-glycine endopeptidase) is a Staphylococcus simulans metalloendopeptidase (crystal structure of lysostaphin). It can function as an antimicrobial against Staphylococcus aureus.[1]

Lysostaphin
Identifiers
EC number3.4.24.75
CAS number9011-93-2
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

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.[2] S. aureus cell walls contain high proportions of pentaglycine, making lysostaphin a highly effective agent against both actively growing and quiescent bacteria.[3]

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.[3] Compared to commonly used antibiotics such as vancomycin, lysostaphin has been shown to demonstrate greater antibacterial activity in vitro.[4] 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.[5] 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.[6] A study published by Belyansky et al. illustrated that a lysostaphin bound mesh demonstrated dramatic preservation results in a rat model.[7]

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 bioflim, therefore eliminating the need for surgical removal of the infected device.[3]

References
  1. Kokai-Kun JF, Walsh SM, Chanturiya T, Mond JJ (May 2003). "Lysostaphin cream eradicates Staphylococcus aureus nasal colonization in a cotton rat model". Antimicrobial Agents and Chemotherapy. 47 (5): 1589–97. doi:10.1128/AAC.47.5.1589-1597.2003. PMC 153340. PMID 12709327.
  2. Schindler CA, Schuhardt VT (Mar 1964). "Lysostaphin: A New Bacteriolytic Agent for the Staphylococcus". Proceedings of the National Academy of Sciences of the United States of America. 51 (3): 414–21. doi:10.1073/pnas.51.3.414. PMC 300087. PMID 14171453.
  3. Wu JA, Kusuma C, Mond JJ, Kokai-Kun JF (Nov 2003). "Lysostaphin disrupts Staphylococcus aureus and Staphylococcus epidermidis biofilms on artificial surfaces". Antimicrobial Agents and Chemotherapy. 47 (11): 3407–14. doi:10.1128/AAC.47.11.3407-3414.2003. PMC 253758. PMID 14576095.
  4. Yang XY, Li CR, Lou RH, Wang YM, Zhang WX, Chen HZ, Huang QS, Han YX, Jiang JD, You XF (Jan 2007). "In vitro activity of recombinant lysostaphin against Staphylococcus aureus isolates from hospitals in Beijing, China". Journal of Medical Microbiology. 56 (Pt 1): 71–6. doi:10.1099/jmm.0.46788-0. PMID 17172520.
  5. Dajcs JJ, Hume EB, Moreau JM, Caballero AR, Cannon BM, O'Callaghan RJ (May 2000). "Lysostaphin treatment of methicillin-resistant Staphylococcus aureus keratitis in the rabbit". Investigative Ophthalmology & Visual Science. 41 (6): 1432–7. PMID 10798659.
  6. Aguinaga A, Francés ML, Del Pozo JL, Alonso M, Serrera A, Lasa I, Leiva J (Jun 2011). "Lysostaphin and clarithromycin: a promising combination for the eradication of Staphylococcus aureus biofilms". International Journal of Antimicrobial Agents. 37 (6): 585–7. doi:10.1016/j.ijantimicag.2011.02.009. hdl:10261/49232. PMID 21497068.
  7. Belyansky I, Tsirline VB, Martin TR, Klima DA, Heath J, Lincourt AE, Satishkumar R, Vertegel A, Heniford BT (Dec 2011). "The addition of lysostaphin dramatically improves survival, protects porcine biomesh from infection, and improves graft tensile shear strength". The Journal of Surgical Research. 171 (2): 409–15. doi:10.1016/j.jss.2011.04.014. PMID 21696759.
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