title: Identification and characterization of novel catalytic bioscavengers of organophosphorus nerve agents.
abstract: In an effort to discover novel catalytic bioscavengers of organophosphorus (OP) nerve agents, cell lysates from a diverse set of bacterial strains were screened for their capacity to hydrolyze the OP nerve agents VX, VR, and soman (GD). The library of bacterial strains was identified using both random and rational approaches. Specifically, two representative strains from eight categories of extremophiles were chosen at random. For the rational approach, the protein sequence of organophosphorus hydrolase (OPH) from Brevundimonas diminuta was searched against a non-redundant protein database using the Basic Local Alignment Search Tool to find regions of local similarity between sequences. Over 15 protein sequences with significant sequence similarity to OPH were identified from a variety of bacterial strains. Some of these matches were based on predicted protein structures derived from bacterial genome sequences rather than from bona fide proteins isolated from bacteria. Of the 25 strains selected for nerve agent testing, three bacterial strains had measurable levels of OP hydrolase activity. These strains are Ammoniphilus oxalaticus, Haloarcula sp., and Micromonospora aurantiaca. Lysates from A. oxalaticus had detectable hydrolysis of VR; Haloarcula sp. had appreciable hydrolysis of VX and VR, whereas lysates from M. aurantiaca had detectable hydrolysis of VR and GD.
authors.affiliation: Neurobehavioral Toxicology Branch, Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, United States. tamara.c.otto@us.army.mil
authors.forename: Tamara C
authors.initials: TC
authors.lastname: Otto
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Scott
authors.forename: Monika A
authors.initials: MA
authors.lastname: Kauffman
authors.forename: Sean M
authors.initials: SM
authors.lastname: Hodgins
authors.forename: Robert C
authors.initials: RC
authors.lastname: Ditargiani
authors.forename: James H
authors.initials: JH
authors.lastname: Hughes
authors.forename: Erin P
authors.initials: EP
authors.lastname: Sarricks
authors.forename: Greg A
authors.initials: GA
authors.lastname: Saturday
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Hamilton
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Cerasoli
mesh_terms: D000931:Antidotes / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D056449:Bacillales / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002619:Chemical Warfare Agents / Q000378:metabolism* / Q000633:toxicity; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D019613:Haloarcula / Q000201:enzymology / Q000235:genetics; D006868:Hydrolysis; D008847:Micromonospora / Q000201:enzymology / Q000235:genetics; D009943:Organophosphorus Compounds / Q000378:metabolism* / Q000633:toxicity; D009946:Organothiophosphorus Compounds / Q000378:metabolism / Q000633:toxicity; D010261:Paraoxon / Q000378:metabolism / Q000633:toxicity; D012999:Soman / Q000378:metabolism / Q000633:toxicity
chemical_list: D000931:Antidotes; D043303:Aryldialkylphosphatase; D001426:Bacterial Proteins; D002619:Chemical Warfare Agents; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; D010261:Paraoxon; D012999:Soman; C009680:VX-agent