Vitamin C potentiates the killing of Mycobacterium tuberculosis by the first-line tuberculosis drugs isoniazid and rifampicin in mice [PublishAheadOfPrint]

The treatment of drug-susceptible tuberculosis (TB) is long and cumbersome. Mismanagement of TB treatment can lead to the emergence of drug resistance in patients, so shortening the treatment duration could significantly improve TB chemotherapy and prevent the development of drug resistance. We had previously discovered that high concentrations of vitamin C sterilize cultures of drug-susceptible and drug-resistant Mycobacterium tuberculosis. Here, we tested sub-inhibitory concentration of vitamin C in combination with TB drugs against M. tuberculosis in vitro and in a mouse model of M. tuberculosis infection. In vivo, we showed that vitamin C level in mouse serum can be increased by intraperitoneal injection of vitamin C to reach vitamin C levels close to the concentrations required for activity in vitro. Although vitamin C had no activity by itself in M. tuberculosis-infected mice, the combination of vitamin C with the first-line TB drugs isoniazid and rifampicin reduced the bacterial burden in the lungs of M. tuberculosis-infected mice faster than isoniazid and rifampicin combined in two independent experiments. These experiments suggest that the addition of vitamin C to first-line TB drugs could shorten TB treatment. Vitamin C, an inexpensive and non-toxic compound, could be easily added to the TB pharmacopeia to substantially improve chemotherapy outcome, which would have a significant impact on the worldwide TB community.

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