Antimicrobial activity of gallium against virulent Rhodococcus equiin vitro and in vivo.
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.
Harrington
J R
JR
Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. rmartens@cvm.tamu.edu
Martens
R J
RJ
Cohen
N D
ND
Bernstein
L R
LR
D000193:Actinomycetales Infections / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D005260:Female; D005708:Gallium / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D016929:Rhodococcus equi / Q000187:drug effects* / Q000472:pathogenicity
D007166:Immunosuppressive Agents; D005708:Gallium; C027235:gallium nitrate