Mechanism of microbicidal action of E-101 solution, a myeloperoxidase-mediated antimicrobial, and its oxidative products

Gerald Denys, Neil C. Devoe, Polyxeni Gudis, Meghan May, Robert C. Allen, Jackson T. Stephens

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 solution. 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 ultrastructure changes and microbicidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Time-kill and transmission electron microscopy studies were also 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 minimal bactericidal concentration (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 that the primary site where E-101 solution exerts microbicidal action is the cell membrane, by inactivation of essential cell membrane components.

Original languageEnglish (US)
Article numbere00261-19
JournalInfection and Immunity
Volume87
Issue number7
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Peroxidase
Glucose Oxidase
Swine
Methicillin-Resistant Staphylococcus aureus
Glutathione
Reactive Oxygen Species
Cell Membrane
Escherichia coli
Hypochlorous Acid
Glucose
Singlet Oxygen
Cellular Structures
Serum
Transmission Electron Microscopy
Sodium Chloride
Hydrogen Peroxide
Amino Acids
Membranes
Enzymes

Keywords

  • Antimicrobial agent
  • E-101 solution
  • Hydrogen peroxide
  • Hypochlorous acid
  • Myeloperoxidase
  • Oxidants
  • Singlet oxygen

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Mechanism of microbicidal action of E-101 solution, a myeloperoxidase-mediated antimicrobial, and its oxidative products. / Denys, Gerald; Devoe, Neil C.; Gudis, Polyxeni; May, Meghan; Allen, Robert C.; Stephens, Jackson T.

In: Infection and Immunity, Vol. 87, No. 7, e00261-19, 01.01.2019.

Research output: Contribution to journalArticle

Denys, Gerald ; Devoe, Neil C. ; Gudis, Polyxeni ; May, Meghan ; Allen, Robert C. ; Stephens, Jackson T. / Mechanism of microbicidal action of E-101 solution, a myeloperoxidase-mediated antimicrobial, and its oxidative products. In: Infection and Immunity. 2019 ; Vol. 87, No. 7.
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