title: Parenteral Administration of Capsule Depolymerase EnvD Prevents Lethal Inhalation Anthrax Infection.
abstract: Left untreated, inhalation anthrax is usually fatal. Vegetative forms of Bacillus anthracis survive in blood and tissues during infection due to elaboration of a protective poly-γ-D-glutamic acid (PDGA) capsule that permits uncontrolled bacterial growth in vivo, eventually leading to overwhelming bacillosis and death. As a measure to counter threats from multidrug-resistant strains, we are evaluating the prophylactic and therapeutic potential of the PDGA depolymerase EnvD, a stable and potent enzyme which rapidly and selectively removes the capsule from the surface of vegetative cells. Repeated intravenous administration of 10 mg/kg recombinant EnvD (rEnvD) to mice infected with lethal doses of B. anthracis Ames spores by inhalation prevented the emergence of symptoms of anthrax and death; all animals survived the 5-day treatment period, and 70% survived to the end of the 14-day observation period. In contrast to results in sham-treated animals, the lungs and spleen of rEnvD-dosed animals were free of gross pathological changes. We conclude that rEnvD has potential as an agent to prevent the emergence of inhalation anthrax in infected animals and is likely to be effective against drug-resistant forms of the pathogen.
authors.affiliation: School of Pharmacy, University College London, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Negus
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kindgom.
authors.forename: Julia
authors.initials: J
authors.lastname: Vipond
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kindgom.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Hatch
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kindgom.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Rayner
authors.affiliation: School of Pharmacy, University College London, London, United Kingdom peter.taylor@ucl.ac.uk.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Taylor
mesh_terms: D061605:Administration, Intravenous; D000336:Aerosols; D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001408:Bacillus anthracis / Q000187:drug effects; D016667:Bacterial Capsules / Q000187:drug effects*; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006207:Half-Life; D008807:Mice, Inbred BALB C; D010447:Peptide Hydrolases / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012141:Respiratory Tract Infections / Q000517:prevention & control*
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D010447:Peptide Hydrolases