The research, published in Nature Communications, indicates that adding vitamin C to existing TB drugs could shorten TB therapy. The finding calls attention to a novel area for drug design.
TB results from infection with the bacterium M. tuberculosis. About 8.7 million people were affected by TB in 2011, according to the World Health Organization (WHO), while approximately 1.4 million died from it.
A recent report indicated that a handheld diagnostic device that was originally developed to diagnose cancer has been adapted to quickly diagnose TB.
An increasing number of people who have infections do not react to TB drugs. An estimated 650,000 people currently have multi-drug resistant TB (MDR-TB), and of these patients, 9% have extensively drug-resistant TB (XDR-TB).
In low and middle income countries, TB is particularly serious. They make up over 95% of TB-related deaths, according to estimates from the WHO.
The surprising discovery came about when the Einstein experts were analyzing how TB bacteria become resistant to isoniazid - a strong first-line drug for tuberculosis.
The team, led by William Jacobs, Jr., Ph.D., professor of microbiology & immunology and of genetics at Einstein, noticed that isoniazid-resistant TB bacteria were lacking in a molecule referred to as mycothiol.
"We hypothesized that TB bacteria that can't make mycothiol might contain more cysteine, an amino acid," explained Dr. Jacobs.
"So, we predicted that if we added isoniazid and cysteine to isoniazid-sensitive M. tuberculosis in culture, the bacteria would develop resistance. Instead, we ended up killing off the culture - something totally unexpected."
The researchers presumed that cysteine was helping to destroy the TB bacteria by operating as a "reducing agent" that elicits the creation of reactive oxygen species - also referred to as free radicals - which can harm DNA.
Dr. Jacobs, a Howard Hughes Medical Institute researcher and a recently elected member of the National Academy of Sciences, said:
"To test this hypothesis, we repeated the experiment using isoniazid and a different reducing agent - vitamin C. The combination of isoniazid and vitamin C sterilized the M. tuberculosis culture. We were then amazed to discover that vitamin C by itself not only sterilized the drug-susceptible TB, but also sterilized MDR-TB and XDR-TB strains."
Dr. Jacobs had to discover the molecular mechanism by which vitamin C exerted its lethal effect in order to give grounds for examining vitamin C in a clinical trial.
After more research, the scientists learned that vitamin C prompted a Fenton reaction, which makes iron react with other molecules to develop reactive oxygen species that destroy the TB bacteria.
Dr. Jacobs concluded:
"We don't know whether vitamin C will work in humans, but we now have a rational basis for doing a clinical trial. It also helps that we know vitamin C is inexpensive, widely available and very safe to use. At the very least, this work shows us a new mechanism that we can exploit to attack TB."
Written by Sarah Glynn