doi:10.1038/nindia.2018.1 Published online 12 January 2018
Vitamin-C, known for its numerous health benefits now gets another feather in its cap, with new research suggesting that when taken with tuberculosis (TB) drugs, the vitamin could help cure the disease in lesser time than standard treatment methods1.
Researchers, led by Jaya Sivaswami Tyagi, at the biotechnology department of the All India Institute of Medical Sciences (AIIMS) in New Delhi, have used ‘network-based gene expression analysis’ to show that vitamin-C "triggers a multifaceted and robust adaptation response in the TB-causing bacteria Mycobacterium tuberculosis (Mtb).”
Standard treatment regimens take six months or more to cure TB. One reason for this is a subpopulation of Mtb that uses a clever survival strategy to trick the drugs that target actively replicating bacteria. This subpopulation enters into a dormant state where it does not divide, thus evading drug action, but is still latently alive and can flare up into active disease anytime.
"Therefore, a major research priority of TB scientists has been to decode the critical survival pathways in dormant tubercle bacilli in order to formulate new approaches for killing these bacteria," Tyagi, told Nature India.
India has the largest number of TB cases in the world at 23% of the global total and bacterial dormancy has been a major impediment to the eradication of the disease.
"When we investigated drug combinations used to treat patients, we found that the four-drug combination – which has pyrazinamide (PZA) plus added vitamin C – could efficiently kill the subpopulations including the tricky dormant bacteria," Tyagi said.
Although vitamin-C is not itself an antibacterial, it synergizes with PZA, a key first line TB drug, to kill dormant and replicating bacteria, negating their tolerance to TB drugs – rifampicin and isoniazid – in combination treatment.
These findings suggest a novel strategy of using vitamin- C as an adjunct to existing drugs to modulate the physiology of tubercle bacilli for enhanced efficacy of combination chemotherapy, the researchers report. They say that Vitamin C-based models can also be used as novel "screening platforms" to test new drugs and drug combinations for accelerating TB treatment.
"The authors have studied detailed mechanisms how Vitamin-C can be an effective and cheap addition to TB therapy," Vikram Saini, microbiologist at the University of Alabama at Birmingham told Nature India. "It has created substantial interest in the US and I believe it will be a very relevant study in the Indian context."
According to the researchers, the effects of vitamin-C in combination treatment were reproduced in an intra-cellular model, more akin to human infection." Based on these findings, we propose a new strategy involving vitamin- C as an adjunctive treatment agent,” the researchers advocate.
1. Sikri, K. et al. Multifaceted remodeling by vitamin C boosts sensitivity of Mycobacterium tuberculosis subpopulations to combination treatment by anti-tubercular drugs. Redox Biol. (2017) doi: 10.1016/j.redox.2017.12.020