Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021311 (Infection)
 38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recombinant mucolytic protein, lysostaphin, was evaluated as a potential intramammary therapeutic for Staphylococcus aureus mastitis in dairy cattle. Lysostaphin, a product of Staphylococcus simulans, enzymatically degrades the cell wall of Staphylococcus aureus and is bactericidal. Thirty Holstein-Freisian dairy cattle in their first lactation were infected with Staphylococcus aureus (Newbould 305, ATCC 29740) in all quarters. Infections were established and monitored for somatic cell counts and Staphylococcus aureus colony-forming units 3 wk prior to subsequent treatment. Infected animals were injected through the teat canal with a single dose of recombinant lysostaphin (dose response 1 to 500 mg) or after three successive p.m. milkings with 100 mg of recombinant lysostaphin in 60 ml of sterile phosphate-buffered saline. Animals were considered cured if the milk remained free of Staphylococcus aureus for a total of 28 milkings after last treatment. Kinetic analysis of immunologically active recombinant lysostaphin demonstrated that a minimum bactericidal concentration was maintained in the milk for up to 36 to 48 h after a single infusion of 100 mg of recombinant lysostaphin. The cure rate of quarters receiving recombinant lysostaphin (100 mg in sterile phosphate-buffered saline, administered over three consecutive p.m. milkings) was 20% compared with 29% for sodium cephapirin in saline and 57% for a commercial antibiotic formulation, respectively. An improved formulation of recombinant lysostaphin may prove to be an effective alternative to antibiotic therapy for bovine mastitis.
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PMID:Lysostaphin: use of a recombinant bactericidal enzyme as a mastitis therapeutic. 178 88

Infection of the mammary gland, in addition to causing animal distress, is a major economic burden of the dairy industry. Staphylococcus aureus is the major contagious mastitis pathogen, accounting for approximately 15-30% of infections, and has proved difficult to control using standard management practices. As a first step toward enhancing mastitis resistance of dairy animals, we report the generation of transgenic mice that secrete a potent anti-staphylococcal protein into milk. The protein, lysostaphin, is a peptidoglycan hydrolase normally produced by Staphylococcus simulans. When the native form is secreted by transfected eukaryotic cells it becomes glycosylated and inactive. However, removal of two glycosylation motifs through engineering asparagine to glutamine codon substitutions enables secretion of Gln(125,232)-lysostaphin, a bioactive variant. Three lines of transgenic mice, in which the 5'-flanking region of the ovine beta-lactoglobulin gene directed the secretion of Gln(125,232)-lysostaphin into milk, exhibit substantial resistance to an intramammary challenge of 104 colony-forming units (c.f.u.) of S. aureus, with the highest expressing line being completely resistant. Milk protein content and profiles of transgenic and nontransgenic mice are similar. These results clearly demonstrate the potential of genetic engineering to combat the most prevalent disease of dairy cattle.
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PMID:Lysostaphin expression in mammary glands confers protection against staphylococcal infection in transgenic mice. 1113 55

Staphylococci often form biofilms, sessile communities of microcolonies encased in an extracellular matrix that adhere to biomedical implants or damaged tissue. Infections associated with biofilms are difficult to treat, and it is estimated that sessile bacteria in biofilms are 1,000 to 1,500 times more resistant to antibiotics than their planktonic counterparts. This antibiotic resistance of biofilms often leads to the failure of conventional antibiotic therapy and necessitates the removal of infected devices. Lysostaphin is a glycylglycine endopeptidase which specifically cleaves the pentaglycine cross bridges found in the staphylococcal peptidoglycan. Lysostaphin kills Staphylococcus aureus within minutes (MIC at which 90% of the strains are inhibited [MIC(90)], 0.001 to 0.064 microg/ml) and is also effective against Staphylococcus epidermidis at higher concentrations (MIC(90), 12.5 to 64 microg/ml). The activity of lysostaphin against staphylococci present in biofilms compared to those of other antibiotics was, however, never explored. Surprisingly, lysostaphin not only killed S. aureus in biofilms but also disrupted the extracellular matrix of S. aureus biofilms in vitro on plastic and glass surfaces at concentrations as low as 1 microg/ml. Scanning electron microscopy confirmed that lysostaphin eradicated both the sessile cells and the extracellular matrix of the biofilm. This disruption of S. aureus biofilms was specific for lysostaphin-sensitive S. aureus, as biofilms of lysostaphin-resistant S. aureus were not affected. High concentrations of oxacillin (400 microg/ml), vancomycin (800 microg/ml), and clindamycin (800 microg/ml) had no effect on the established S. aureus biofilms in this system, even after 24 h. Higher concentrations of lysostaphin also disrupted S. epidermidis biofilms.
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PMID:Lysostaphin disrupts Staphylococcus aureus and Staphylococcus epidermidis biofilms on artificial surfaces. 1457 95

Infection with antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) is one of the primary causes of hospitalizations and deaths. To address this issue, we have designed antimicrobial coatings incorporating carbon nanotube-enzyme conjugates that are highly effective against antibiotic-resistant pathogens. Specifically, we incorporated conjugates of carbon nanotubes with lysostaphin, a cell wall degrading enzyme, into films to impart bactericidal properties against Staphylococcus aureus and Staphylococcus epidermidis. We fabricated and characterized nanocomposites containing different conjugate formulations and enzyme loadings. These enzyme-based composites were highly efficient in killing MRSA (>99% within 2 h) without release of the enzyme into solution. Additionally, these films were reusable and stable under dry storage conditions for a month. Such enzyme-based film formulations may be used to prevent growth of pathogenic and antibiotic-resistant microorganisms on various common surfaces in hospital settings. Polymer and paint films containing such antimicrobial conjugates, in particular, could be advantageous to prevent risk of staphylococcal-specific infection and biofouling.
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PMID:Antistaphylococcal nanocomposite films based on enzyme-nanotube conjugates. 2060 74

Lysostaphin is an antimicrobial agent belonging to a major class of antimicrobial peptides and proteins known as the bacteriocins. Bacteriocins are bacterial antimicrobial peptides which generally exhibit bactericidal activity against other bacteria. Bacteriocin production is a self-protection mechanism that helps the microorganisms to survive in their natural habitats. Bacteriocins are currently distributed into three main classes. Staphylococcins are bacteriocins produced by staphylococci, which are Gram-positive bacteria of medical and veterinary importance. Lysostaphin is the only class III staphylococcin described so far. It exhibits a high degree of antistaphylococcal bacteriolytic activity, being inactive against bacteria of all other genera. Infections caused by staphylococci continue to be a problem worldwide not only in healthcare environments but also in the community, requiring effective measures for controlling their spread. Since lysostaphin kills human and animal staphylococcal pathogens, it has potential biotechnological applications in the treatment of staphylococcal infections. In vitro and in vivo studies performed with lysostaphin have shown that this staphylococcin has potential to be used, solely or in combination with other antibacterial agents, to prevent or treat bacterial staphylococcal infectious diseases.
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PMID:Lysostaphin: A Staphylococcal Bacteriolysin with Potential Clinical Applications. 2771 93

Staphylococcus aureus is the most common pathogen associated with bacterial infections in orthopedic procedures. Infections often lead to implant failure and subsequent removal, motivating the development of bifunctional materials that both promote repair and prevent failure due to infection. Lysostaphin is an anti-staphylococcal enzyme resulting in bacterial lysis and biofilm reduction. Lysostaphin use is limited by the lack of effective delivery methods to provide sustained, high doses of enzyme to infection sites. We engineered a BMP-2-loaded lysostaphin-delivering hydrogel that simultaneously prevents S. aureus infection and repairs nonhealing segmental bone defects in the murine radius. Lysostaphin-delivering hydrogels eradicated S. aureus infection and resulted in mechanically competent bone. Cytokine and immune cell profiling demonstrated that lysostaphin-delivering hydrogels restored the local inflammatory environment to that of a sterile injury. These results show that BMP-2-loaded lysostaphin-delivering hydrogel therapy effectively eliminates S. aureus infection while simultaneously regenerating functional bone resulting in defect healing.
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PMID:Lysostaphin and BMP-2 co-delivery reduces S. aureus infection and regenerates critical-sized segmental bone defects. 3111 4