Effects of (1-Decyl)triphenylphosphonium on Mycobacterium tuberculosis infections in vitro and in vivo
Quattlebaum, Sarah Elizabeth
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Mycobacterium tuberculosis is the greatest cause of infectious disease by a single agent, and expresses multiple virulence factors to avoid destruction and maintain residence inside the host cell to survive, replicate, and avoid immune system detection. M. tuberculosis is difficult to target with antibiotics, and many strains are emerging as multidrug-resistant. (1-Decyl)triphenylphosphonium (dTPP) has been used in many previous studies, and the purpose of this study was to investigate antimycobacterial efficacy and cytotoxic effects of dTPP in murine bone marrow-derived macrophages. Bacterial load was significantly reduced by dTPP treatment, but the compound also exerted significant cytotoxic effects in vitro. Efficacy and safety of dTPP usage in vivo also were tested using a murine model to determine synergistic effects when combined with a known antimycobacterial agent, Rifampin. Within 24-hours of treatment with dTPP, all mice were dead or presented with neurologic signs upon physical examination. This is the first study reporting adverse effects of dTPP.