Antimicrobial activity of gallium against virulent Rhodococcus equiin vitro and in vivo

被引:70
作者
Harrington, JR
Martens, RJ [1 ]
Cohen, ND
Bernstein, LR
机构
[1] Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Large Anim Clin Sci, College Stn, TX 77843 USA
[2] Terrametrix, Menlo Pk, CA USA
关键词
D O I
10.1111/j.1365-2885.2006.00723.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Rhodococcus equi, a facultative intracellular bacterium, causes severe pneumonia in foals. Evidence suggests that most foals become infected very early in life, when they have immature or ineffective innate immune responses. This study evaluated the antimicrobial activity of gallium against R. equi, as a potential chemoprophylactic and therapeutic agent. Rhodococcus equi was grown in media with various concentrations of gallium nitrate (GN), with and without excess iron. GN significantly inhibited growth and killed R. equi, and these effects were abolished with excess iron. Antimicrobial effects of Ga appear to be related to its interference with iron metabolism. Mice were treated orally with gallium maltolate (GaM), 10 or 50 mg/kg BW, or distilled H2O prior to and after experimental infection with R. equi. Six days post-infection, organs were harvested and R. equi concentrations assessed, and serum gallium concentrations determined. GaM was absorbed in a dose-dependent manner, and R. equi tissue burdens were greater in control mice than in all GaM-treated mice. GaM may aid in the control of disease by preventing development of overwhelming R. equi tissue burdens prior to the establishment of requisite innate and adaptive immune responses.
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收藏
页码:121 / 127
页数:7
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