Lysostaphin (, ''glycyl-glycine endopeptidase'') is a ''
Staphylococcus simulans''
metalloendopeptidase A metalloendopeptidase is an enzyme that functions as a metalloproteinase endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids (i.e. within the molecule), in contrast to exop ...
crystal structure of lysostaphin. It can function as a
bacteriocin
Bacteriocins are proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally, and ec ...
(antimicrobial) against ''
Staphylococcus aureus''.
Lysostaphin is a 27 KDa
glycylglycine
Glycylglycine is the dipeptide of glycine, making it the simplest peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are call ...
endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids (i.e. within the molecule), in contrast to exopeptidases, which break peptide bonds from end-pieces of terminal amino acids. For this ...
, an
antibacterial
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
which is capable of cleaving the crosslinking
pentaglycine bridges found in the cell wall
peptidoglycan
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...
of certain ''Staphylococci''. Lysostaphin was first isolated from a culture of ''Staphylococcus simulans'' by Schindler and Schuhardt in 1964. ''S. aureus'' cell walls contain high proportions of pentaglycine, 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
A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...
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.
Compared to commonly used antibiotics such as
vancomycin
Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...
, lysostaphin 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
Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...
) mediated
keratitis
Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...
''in vivo'' in a rabbit model. Additionally, it has been shown that lysostaphin combined with antimicrobials such as
cefazolin
Cefazolin, also known as cefazoline and cephazolin, is a first-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. Specifically it is used to treat cellulitis, urinary tract infections, pneumonia, e ...
,
clarithromycin
Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, '' H. pylori'' infection, and Lyme disease, among others. Clarith ...
,
doxycycline,
levofloxacin
Levofloxacin, sold under the brand name Levaquin among others, is an antibiotic medication. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori (in combination with other medications), ...
,
linezolid
Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, v ...
and
quinuprisitin/
dalfopristin
Dalfopristin is a semi-synthetic streptogramin antibiotic analogue of ostreogyrcin A ( virginiamycin M, pristinamycin IIA, streptogramin A). The combination quinupristin/dalfopristin (marketed under the trade name Synercid) was brought to th ...
has a synergistic effect for MSSA strains of the bacteria.
A study published by Belyansky et al. illustrated that a lysostaphin bound mesh demonstrated dramatic preservation results in a rat model.
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.
References
External links
* The
MEROPS
MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibit ...
online database for peptidases and their inhibitors
M23.004*
*
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EC 3.4.24
Bacteriocins