Lysostaphin
Encyclopedia
Lysostaphin is a Staphylococcus simulans metalloendopeptidase
. It can function as an antimicrobial against Staphylococcus aureus
.
Lysostaphin is a 27 KDa glycylglycine
endopeptidase
, an antibacterial enzyme
which is capable of cleaving the crosslinking pentaglycin bridges in the cell wall of Staphylococci. Lysotaphin was first isolated from a culture of Staphylococcus simulans by Schindler and Schuhardt in 1964. S. aureus cell walls contain high proportions of pentaglycin, making lysostaphin a highly effective agent against both actively growing and quiescent bacteria.
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 lypsotaphin since its isolation, both in vitro and in vivo. Lypsostaphin 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. Compared to commonly used antibiotics such as vancomycin
, lysotaphin has been shown to demonstrate greater antibacterial activity in vitro. 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. 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 MMSA strains of the bacteria. Recently, a study published by Belyansky et al. illustrated that a lysostaphin bound mesh demonstrated dramatic preservation results in a rat model.
Using lyosptaphin 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 .
Metalloendopeptidase
A metalloendopeptidase is an enzyme that functions as a metalloproteinase endopeptidase....
. It can function as an antimicrobial against Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
.
Lysostaphin is a 27 KDa glycylglycine
Glycylglycine
Glycylglycine is the dipeptide of glycine, making it the simplest peptide.The compound was first synthesized by Emil Fischer and Ernest Fourneau in 1901 by boiling 2,5-diketopiperazine with hydrochloric acid....
endopeptidase
Endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids , in contrast to exopeptidases, which break peptide bonds from their end-pieces. For this reason, endopeptidases cannot break down peptides into monomers, while exopeptidases can break...
, an antibacterial enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
which is capable of cleaving the crosslinking pentaglycin bridges in the cell wall of Staphylococci. Lysotaphin was first isolated from a culture of Staphylococcus simulans by Schindler and Schuhardt in 1964. S. aureus cell walls contain high proportions of pentaglycin, making lysostaphin a highly effective agent against both actively growing and quiescent bacteria.
Staphylococcal infections of both Staphylococcus aureus and Staphylococcus epidermidis
Staphylococcus epidermidis
Staphylococcus epidermidis is one of thirty-three known species belonging to the genus Staphylococcus. It is part of human skin flora, and consequently part of human flora. It can also be found in the mucous membranes and in animals. Due to contamination, it is probably the most common species...
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
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...
on implantable devices. Once a "Staphylococcal" biofilm has formed on an implanted medical device, it is difficult to disrupt due to its antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
and protection against bacterial action.
Many studies have been previously published on lypsotaphin since its isolation, both in vitro and in vivo. Lypsostaphin 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. Compared to commonly used antibiotics such as vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
, lysotaphin has been shown to demonstrate greater antibacterial activity in vitro. The enzyme has demonstrated effectiveness against methicillin susceptible S. aureus (MSSA
MSSA
MSSA may refer to* Methicillin-sensitive Staphylococcus aureus, a kind of bacteria* MSSA Chemical company, a French chemical company, also known as Métaux Spéciaux* Military-style semi-automatic, a firearm...
) and methicillin resistant S. aureus (MRSA) mediated keratitis
Keratitis
Keratitis is a condition in which the eye's cornea, the front part of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves impaired eyesight.-Types:...
in vivo in a rabbit model. Additionally, it has been shown that lysostaphin combined with antimicrobials such as cefazolin
Cefazolin
Cefazolin , also known as cefazoline or cephazolin, is a first-generation cephalosporin antibiotic.The drug is usually administrated by either intramuscular injection or intravenous infusion .-Indications:Cefazolin is mainly used to treat bacterial infections of the skin...
, clarithromycin
Clarithromycin
Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia , skin and skin structure infections...
, doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
, levofloxacin
Levofloxacin
Levofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class and is used to treat severe or life-threatening bacterial infections or bacterial infections that have failed to respond to other antibiotic classes. It is sold under various brand names, such as Levaquin and...
, linezolid
Linezolid
Linezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
and quinuprisitin/dalfopristin
Dalfopristin
Dalfopristin is a streptogramin antibiotic derived from pristinamycin IIA. The combination quinupristin/dalfopristin, in a weight-to-weight ratio of 30% quinupristin to 70% dalfopristin, is used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium....
has a synergistic effect for MMSA strains of the bacteria. Recently, a study published by Belyansky et al. illustrated that a lysostaphin bound mesh demonstrated dramatic preservation results in a rat model.
Using lyosptaphin 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 .
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: M23.004