The in Vitro Effect of Lysostaphin on Clinical Isolates of Staphylococcus Aureus

Cb, Cropp; Ef, Harrison

doi:10.1139/m64-107

Cited by 23 publications

(10 citation statements)

References 6 publications

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“…21 This enzymatic cleavage leads to destabilization of the staphylococcal cell wall, loss of osmotic equilibrium and rapid lysis of the staphylococci, often within seconds. 22 Lysostaphin is highly effective against both rapidly dividing S. aureus as well as quiescent cells, 4 and recently we have demonstrated that lysostaphin will also lyse staphylococci in biofilms killing both the sessile cells as well as disrupting the extracellular biofilm matrix. 19 A few early studies examined the potential of nonrecombinant lysostaphin, purified from S. simulans, as a therapy for S. aureus infection in animal models.…”

Section: Introductionmentioning

confidence: 99%

Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model

Kokai‐Kun¹,

Chanturiya²,

Mond³

2007

Journal of Antimicrobial Chemotherapy

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Objectives: With the isolation of clinical strains of Staphylococcus aureus carrying the gene that confers vancomycin resistance, the need for novel antistaphylococcals has become more urgent. Lysostaphin, an example of such a novel therapeutic, is an endopeptidase that rapidly lyses S. aureus through proteolysis of the staphylococcal cell wall. We evaluated its efficacy as a therapeutic agent for treatment of systemic S. aureus infection in a mouse model. Methods:Mice (5-10 per group) challenged with methicillin-susceptible S. aureus developed bacteraemia and organ infections while mice challenged with methicillin-resistant S. aureus (MRSA) developed organ infections. The challenged mice received various intravenous doses of recombinant lysostaphin, administered once a day for 1-3 days when compared with treatment with oxacillin or vancomycin. Some mice also received treatment of lysostaphin combined with oxacillin or vancomycin. Following treatment, bacteraemia was determined, and mice were sacrificed and organ infection was determined.Results and conclusions: Lysostaphin administered at 5 mg/kg once a day for 3 days consistently cleared S. aureus from the blood and the organs of infected mice. Furthermore, the combination of lysostaphin and oxacillin or vancomycin demonstrated increased efficacy against MRSA over lysostaphin alone allowing the therapeutic dose of lysostaphin to be reduced to 1 mg/kg. These results demonstrate that lysostaphin is an effective treatment for eradicating S. aureus from the blood and from the organs of infected mice.

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Section: Introductionmentioning

confidence: 99%

Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model

Kokai‐Kun¹,

Chanturiya²,

Mond³

2007

Journal of Antimicrobial Chemotherapy

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“…Recent reports on the discovery and antistaphylococcal specificity of lysostaphin (Schindler and ), on its purification (Shindler and Schuhardt, 1965), on its utility against a large number of clinical strains of Staphylococcus aureus both in vitro (Schindler and Schuhardt, 1964;Cropp and Harrison, 1964;Harrison and Cropp, 1965) and in vivo (Schuhardt and Schindler, 1964), and on its enzymatic mode of action (Browder et al, Biochem. Biophys.…”

mentioning

confidence: 99%

Microbiological Activities of Lysostaphin and Penicillins Against Bacteriophage 80/81 Strains of Staphylococcus aureus

Zygmunt¹,

Harrison²,

Browder³

1965

Applied Microbiology

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activities of lysostaphin and penicillins against bacteriophage 80/81 strains of Staphylococcus aureus. Appl. Microbiol. 13:491-493. 1965.-Using 20 clinical isolates of S. aureus (all bacteriophage 80/81 type), we found that lysostaphin inhibits the growth of all cultures at concentrations significantly lower than those observed with any of eight penicillins, a penicillin-like compound (cephalothin), or fusidic acid (a steroid antibiotic). All test cultures were shown to be resistant to penicillin G, ampicillin, and propicillin. Of the remaining penicillins (all penicillinase-insensitive), oxacillin, nafcillin, cloxacillin, and cephalothin were approximately equal in antimicrobial activity. Ancillin was slightly less active, and methicillin was even lower in potency. Cultures varied more widely in susceptibility to fusidic acid. None of the clinical isolates tested was found to be resistant to lysostaphin.

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“…A second enzyme is an acetylmuramic acid-L-alanine amidase which appears not to be bacteriolytic, per se, but only capable of acting on previously solubilized peptidoglycan (24). The major component in lysostaphin is a glycylglycine endopeptidase which is capable of specifically lysing staphylococcal cells, especially those of S. aureus (4,11,12).…”

mentioning

confidence: 99%

Relationship between lysostaphin endopeptidase production and cell wall composition in Staphylococcus staphylolyticus

Robinson¹,

Hardman²,

Sloan³

1979

J Bacteriol

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Mutants of Staphylococcus staphylolyticus incapable of producing an extracellular staphylolytic glycylglycine endopeptidase were isolated and found to have cells in the population susceptible to lysis by this enzyme, as did the wild-type organism under conditions in which the endopeptidase was not produced. These results suggest that cultures of this organism normally contain a heterogeneous population of cells with regard to cell wall composition and susceptibility to the enzyme. Production of the endopeptidase appears to act as a selective pressure which removes the susceptible cells in the population as the enzyme appears in the medium. A comparison of the peptidoglycan of the wild-type organism grown under conditions in which the endopeptidase was produced with that of this organism grown under nonproducing conditions and with those of endopeptidaseless mutants showed that in the presence of the endopeptidase the cell population had peptidoglycan with shorter peptide cross bridges and a greater percentage of serine in these cross bridges than was found in cells grown in the absence of the enzyme. The inability of the endopeptidase to hydrolyze glycylserine and serylglycine peptide bonds suggests that at least part of the resistance this organism has to the endopeptidase is due to relative amounts of serine found in the peptide cross bridges of some cells in the population.

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The in Vitro Effect of Lysostaphin on Clinical Isolates of Staphylococcus Aureus

Cited by 23 publications

References 6 publications

Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model

Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model

Microbiological Activities of Lysostaphin and Penicillins Against Bacteriophage 80/81 Strains of Staphylococcus aureus

Relationship between lysostaphin endopeptidase production and cell wall composition in Staphylococcus staphylolyticus

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