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Vitamin C Kills Drug-Resistant TB

Researchers find new way to attack infection (May 21)

In an unexpected discovery, researchers at Albert Einstein College of Medicine of Yeshiva University have found that vitamin C kills drug-resistant tuberculosis (TB) bacteria in laboratory culture. The finding suggests that vitamin C added to existing TB drugs could shorten TB therapy, and it highlights a new area for drug design.

The study was published May 21 in the online journal Nature Communications.

The discovery occurred during research into how TB bacteria become resistant to isoniazid, a potent first-line TB drug. Lead investigator William Jacobs, Jr., PhD, and colleagues observed that isoniazid-resistant TB bacteria were deficient in a molecule called mycothiol.

“We hypothesized that TB bacteria that can’t make mycothiol might contain more cysteine, an amino acid,” Jacobs said. “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 suspected that cysteine was helping to kill TB bacteria by acting as a “reducing agent” that triggers the production of reactive oxygen species (sometimes called free radicals), which can damage DNA.

“To test this hypothesis, we repeated the experiment using isoniazid and a different reducing agent — vitamin C,” Jacobs remarked. “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.”

To justify testing vitamin C in a clinical trial, Jacobs needed to find the molecular mechanism by which vitamin C exerted its lethal effect. More research produced the answer: Vitamin C induced what is known as a Fenton reaction, causing iron to react with other molecules to create reactive oxygen species that kill the TB bacteria.

“We don’t know whether vitamin C will work in humans, but we now have a rational basis for doing a clinical trial,” Jacobs said. “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.”

Source: Albert Einstein College of Medicine; May 21, 2013.

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