Deferoxamine as adjunct therapeutics for tuberculosis

Abstract

Iron is a critical element used for survival of both host and pathogens. Tuberculosis patients show dysregulated iron metabolism and provide an opportunity for developing host directed therapeutics. In this study, C57BL/6 mice supplemented with ferric carboxymaltose and controls were aerosol infected with 100-120 CFU of the H37Rv strain of Mycobacterium tuberculosis. A subgroup of mice received deferoxamine (DFO) with or without isoniazid and rifampicin. The iron supplemented C57BL/6 mice showed higher tissue mycobacterial burden at 2 weeks of post infection. The efficacy of isoniazid and rifampicin was compromised in iron supplemented C57BL/6 mice. Iron chelation by deferoxamine (DFO) alone for a month significantly reduced the tissue mycobacterial burden but was less effective in the iron-supplemented group. DFO as an adjunct to isoniazid and rifampicin cleared the tissue mycobacteria more efficiently. Currently, DFO is used for treating acute iron poisoning and iron overloaded thalassemic patients and holds promise as an adjunct therapeutic agent for TB.