Effect of the Mammalian Arginase Inhibitor 2(<Emphasis Type="Italic">S</Emphasis>)-Amino-6-Boronohexanoic Acid on <Emphasis Type="Italic">Bacillus anthracis</Emphasis> Arginase |
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Authors: | Pei?Tsai Guan-Liang?Cao Bruce?Tomczuk Peter?D?Suzdak Alan?S?Cross Paul?Shapiro Email author" target="_blank">Gerald?M?RosenEmail author |
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Institution: | (1) Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 North Pine St., Baltimore, MD 21201, USA;(2) Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, MD 21201, USA;(3) Corridor Pharmaceuticals, Inc, Baltimore, MD 21093, USA;(4) Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; |
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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. |
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