Therapeutic applications of lysostaphin against Staphylococcus aureus

Abstract

Staphylococcus aureus, an opportunistic pathogen, causes diverse community and nosocomial-acquired human infections, including folliculitis, impetigo, sepsis, septic arthritis, endocarditis, osteomyelitis, implant-associated biofilm infections and contagious mastitis in cattle. In recent days, both methicillinsensitive and methicillin-resistant S. aureus infections have increased. Highly effective anti-staphylococcal agents are urgently required. Lysostaphin is a 27 kDa zinc metallo antimicrobial lytic enzyme that is produced by Staphylococcus simulans biovar staphylolyticus and was first discovered in the 1960s. Lysostaphin is highly active against S. aureus strains irrespective of their drug-resistant patterns with a minimum inhibitory concentration of ranges between 0Á001 and 0Á064 lg ml À1 . Lysostaphin has activity against both dividing and non-dividing S. aureus cells; and can seep through the extracellular matrix to kill the biofilm embedded S. aureus. In spite of having excellent anti-staphylococcal activity, its clinical application is hindered because of its immunogenicity and reduced bio-availability. Extensive research with lysostaphin lead to the development of several engineered lysostaphin derivatives with reduced immunogenicity and increased serum half-life. Therapeutic efficacy of both native and engineered lysostaphin derivatives was studied by several research groups. This review provides an overview of the therapeutic applications of native and engineered lysostaphin derivatives developed to eradicate S. aureus infections.

Screening and in Silico Validation of Anti-Microbial Peptides Derived from Lysostaphin, Entero and Endolysin

“…Bacteriocins are antimicrobial proteins exhibiting bactericidal activity against other bacterial species. This endopeptidase derived from Staphylococcus simulans was found to break the peptidoglycan bridge [15]. Enterolysin is a protein purified from Enterococcus faecalis.…”

Combating Infectious Diseases with Synthetic Biology

“… 11 Garrido et al first attenuated the bacterium to mediate its in vivo application and tested it in catheter-associated biofilms. Therapeutic elements dispersin B (DspB) and lysostaphin, a bacteriocin shown to be primarily active against methicillin-resistant S. aureus , 31 , 32 were introduced into the attenuated strain via a gene platform. To mediate efficient secretion of the therapeutic elements, they identified and optimized a secretion signal, mnp140Opt , within their attenuated strain.…”

Current Knowledge of the Mode of Action and Immunity Mechanisms of LAB-Bacteriocins

“…Active against Staphylococcus aureus and other pathogens of endometritis sows [42,43] As mentioned above, LAB-bacteriocins have been shown to display multiple biological functions [9,10]. Nonetheless, replacement of traditional antibiotics or potentiating their activity is timely, because of the increasing antimicrobial resistance in the globe and the lack, in some cases, of therapeutic alternatives.…”