title: Effect of the mammalian arginase inhibitor 2(S)-amino-6-boronohexanoic acid on Bacillus anthracis arginase.
abstract: Macrophages, upon phagocytosing endospores of Bacillus anthracis, up-regulate the expression of the immunological isoform of nitric oxide synthase, NOS 2, concomitant with production of nitric oxide (NO•) from metabolism of L -arginine. We have previously demonstrated that macrophages that secrete NO• kill the bacilli of B. anthracis. To circumvent this microbicidal activity of NO•, B. anthracis has evolved pathways that include the enzyme arginase, which metabolizes L: -arginine to ornithine and urea. Compounds that inhibit arginase might, therefore, offer a therapeutic approach to controlling B. anthracis infection. 2(S)-Amino-6-boronohexanoic acid (ABH) has been reported to be an inhibitor of mammalian arginase. In this study, we explore the inhibitory effect of ABH against B. anthracis arginase and its potential for future development, as an effective therapeutic agent against microbial infection. We found that ABH is an inhibitor of bacterial arginase in several different endospore strains of B. anthracis. Further, ABH inhibits neither the phagocytosis of these endospores nor the up-regulation of NOS 2 concomitant with secretion of NO•. These findings set the stage to determine how efficacious ABH will be in promoting NO•-mediating killing of B. anthracis.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Tsai
authors.forename: Guan-Liang
authors.initials: GL
authors.lastname: Cao
authors.forename: Bruce
authors.initials: B
authors.lastname: Tomczuk
authors.forename: Peter D
authors.initials: PD
authors.lastname: Suzdak
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cross
authors.forename: Paul
authors.initials: P
authors.lastname: Shapiro
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rosen
mesh_terms: D000614:Aminocaproates / Q000378:metabolism*; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors*; D001408:Bacillus anthracis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D001896:Boron Compounds / Q000378:metabolism*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice
chemical_list: C121228:2-amino-6-boronohexanoic acid; D000614:Aminocaproates; D001426:Bacterial Proteins; D001896:Boron Compounds; D004791:Enzyme Inhibitors; D001119:Arginase