4 research outputs found

    Protective efficacy of catalytic bioscavenger, paraoxonase 1 against sarin and soman exposure in guinea pigs

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    Human paraoxonase 1 (PON1) has been portrayed as a catalytic bioscavenger which can hydrolyze large amounts of chemical warfare nerve agents (CWNAs) and organophosphate (OP) pesticides compared to the stoichiometric bioscavengers such as butyrylcholinesterase. We evaluated the protective efficacy of purified human and rabbit serum PON1 against nerve agents sarin and soman in guinea pigs. Catalytically active PON1 purified from human and rabbit serum was intravenously injected to guinea pigs, which were 30 min later exposed to 1.2 × LCt50 sarin or soman using a microinstillation inhalation exposure technology. Pre-treatment with 5 units of purified human and rabbit serum PON1 showed mild to moderate increase in the activity of blood PON1, but significantly increased the survival rate with reduced symptoms of CWNA exposure. Although PON1 is expected to be catalytic, sarin and soman exposure resulted in a significant reduction in blood PON1 activity. However, the blood levels of PON1 in pre-treated animals after exposure to nerve agent were higher than that of untreated control animals. The activity of blood acetylcholinesterase and butyrylcholinesterase and brain acetylcholinesterase was significantly higher in PON1 pre-treated animals and were highly correlated with the survival rate. Blood O2 saturation, pulse rate and respiratory dynamics were normalized in animals treated with PON1 compared to controls. These results demonstrate that purified human and rabbit serum PON1 significantly protect against sarin and soman exposure in guinea pigs and support the development of PON1 as a catalytic bioscavenger for protection against lethal exposure to CWNAs

    Extracellular polymeric substance (EPS)-degrading enzymes reduce staphylococcal surface attachment and biocide resistance on pig skin in vivo.

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    Staphylococcal extracellular polymeric substances (EPS) such as extracellular DNA (eDNA) and poly-N-acetylglucosamine surface polysaccharide (PNAG) mediate numerous virulence traits including host colonization and antimicrobial resistance. Previous studies showed that EPS-degrading enzymes increase staphylococcal biocide susceptibility in vitro and in vivo, and decrease virulence in animal models. In the present study we tested the effect of EPS-degrading enzymes on staphylococcal skin colonization and povidone iodine susceptibility using a novel in vivo pig model that enabled us to colonize and treat 96 isolated areas of skin on a single animal in vivo. To quantitate skin colonization, punch biopsies of colonized areas were homogenized, diluted, and plated on agar for colony forming unit enumeration. Skin was colonized with either Staphylococcus epidermidis or Staphylococcus aureus. Two EPS-degrading enzymes, DNase I and the PNAG-degrading enzyme dispersin B, were employed. Enzymes were tested for their ability to inhibit skin colonization and detach preattached bacteria. The effect of enzymes on the susceptibility of preattached S. aureus to killing by povidone iodine was also measured. We found that dispersin B significantly inhibited skin colonization by S. epidermidis and detached preattached S. epidermidis cells from skin. A cocktail of dispersin B and DNase I detached preattached S. aureus cells from skin and increased their susceptibility to killing by povidone iodine. These findings suggest that staphylococcal EPS components such as eDNA and PNAG contribute to skin colonization and biocide resistance in vivo. EPS-degrading enzymes may be a useful adjunct to conventional skin antisepsis procedures in order to further reduce skin bioburden
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