Lysostaphin: an antistaphylococcal agent

Abstract

Lysostaphin is a zinc metalloenzyme which has a specific lytic action against Staphylococcus aureus. Lysostaphin has activities of three enzymes namely, glycylglycine endopeptidase, endo-beta-N-acetyl glucosamidase and N-acteyl muramyl-L-alanine amidase. Glycylglycine endopeptidase specifically cleaves the glycine-glycine bonds, unique to the interpeptide cross-bridge of the S. aureus cell wall. Due to its unique specificity, lysostaphin could have high potential in the treatment of antibiotic-resistant staphylococcal infections. This review article presents a current understanding of the lysostaphin and its applications in therapeutic agent as a treatment against antibiotic-resistant S. aureus and methicillin-resistant S. aureus (MRSA) infections, either alone or in combination with other antibiotics.

Bactericidal synergy of lysostaphin in combination with antimicrobial peptides

“…Lysostaphin kills staphylococcal bacteria by cleaving the pentaglycine bridges in the cell wall [3,31], while most of the peptides used in this present study act against bacteria by affecting the integrity and functioning of the cell membrane [e.g. 25,[32][33][34][35][36][37].…”

“…Since the 1960s, one compound that has attracted attention as a potential anti-staphylococcal treatment is the endopeptidase lysostaphin [1,2]. This 27 kDa enzyme specifically cleaves crosslinking pentaglycine bridges that are found exclusively in the staphylococcal cell wall [3]. Staphylococcus aureus is particularly susceptible to lysostaphin due to the very high proportion of pentaglycine bridges found within its cell wall [3].…”

“…This 27 kDa enzyme specifically cleaves crosslinking pentaglycine bridges that are found exclusively in the staphylococcal cell wall [3]. Staphylococcus aureus is particularly susceptible to lysostaphin due to the very high proportion of pentaglycine bridges found within its cell wall [3]. Historically, lysostaphin suffered from problems with immunogenicity and reliability of supply but these issues have been resolved thanks to new technologies meaning that highly pure enzyme can be produced in great quantities [4][5][6].…”

“…Historically, lysostaphin suffered from problems with immunogenicity and reliability of supply but these issues have been resolved thanks to new technologies meaning that highly pure enzyme can be produced in great quantities [4][5][6]. This has seen renewed interest in using lysostaphin for antimicrobial applications [3,[7][8][9][10][11]. Nonetheless, one drawback with lysostaphin is the high preponderance for bacterial resistance to be selected through mutations in lyrA or the fem operon [12][13][14].…”

Enzybiotics and their Potential Applications in Medicine

“…Lysostaphin is very effi cient in lysing S. aureus and can kill practically all strains of this species, including MRSA (von Eiff et al 2003 ) and strains with reduced susceptibility to vancomycin (Patron et al 1999 ). However, its activity against coagulase -negative staphylococci is essentially weaker due to a different amino acid composition of their cross -bridges (Kumar 2008 ). Aside from planktonic staphylococcal cells, lysostaphin can also specifi cally eliminate staphylococcal biofi lms (Wu et al 2003 ).…”