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bioRxiv · 10.1101/394114

Mechanism of Microbicidal Action of E-101 Solution, a Myeloperoxidase-Mediated Antimicrobial, and its Oxidative Products

Denys, G. A.·Devoe, N. C.·Gudis, P.·May, M.·Allen, R.·Stephens, J. T.
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Abstract

E-101 Solution is a first in class myeloperoxidase-mediated antimicrobial developed for topical application. It is composed of porcine myeloperoxidase (pMPO), glucose oxidase (GO), glucose, sodium chloride, and specific amino acids in an aqueous vehicle. Once activated, the reactive species hydrogen peroxide (H2O2), hypochlorous acid and singlet oxygen are generated. We evaluated the treatment effects of E-101 solution and its oxidative products on ultrastucture changes and microbicidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Time kill and transmission electron microscopy studies were performed using formulations with pMPO or GO omitted. The glutathione membrane protection assay was used to study the neutralization of reactive oxygen species. The potency of E-101 solution was also measured in the presence of serum and whole blood by MIC and MBC determinations. E-101 solution demonstrated rapid bactericidal activity and ultracellular changes in MRSA and E. coli cells. When pMPO was omitted, high levels of H2O2 generated from GO and glucose demonstrated slow microbicidal activity with minimal cellular damage. When GO was omitted from the formulation no antimicrobial activity or cellular damage was observed. Protection from exposure to E-101 solution reactive oxygen species in the glutathione protection assay was competitive and temporary. E-101 solution maintained its antimicrobial activity in the presence of inhibitory substances such as serum and whole blood. E-101 solution is a potent myeloperoxidase enzyme system with multiple oxidative mechanisms of action. Our findings suggest the primary site that E-101solution exerts microbicidal action is the cell membrane by inactivation of essential cell membrane components.

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Denys, G. A., Devoe, N. C., Gudis, P., May, M., Allen, R., Stephens, J. T.. 2018-08-17. Mechanism of Microbicidal Action of E-101 Solution, a Myeloperoxidase-Mediated Antimicrobial, and its Oxidative Products. https://doi.org/10.1101/394114

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