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Vitamin C hits hard when bacteria is under stress, finds study

Photo: Sudhira H S/Research Matters

A new study by researchers from the Indian Institute of Science, Bengaluru has given us one more reason to use oranges, lemons and other foods rich in vitamin C. Known to increase our immunity and protect us from infection, doctors routinely prescribe vitamin C tablets for patients to fight off bacterial infections. But why? This study has revealed the molecular mechanism behind why vitamin C and bacteria do not go well together.

During times of stress such as scarcity of nutrients like amino acids, fatty acids etc. or presence of antibiotics, most types of bacteria wisely shut down their fundamental processes. Instead, they divert the energy and resources for survival. This, they do with the help of an enzyme called ‘Rel’ which produces a molecule called (p)ppGpp - a slightly modified form of Guanine nucleotide, a basic building block of DNA. This (p)ppGpp is appropriately named ‘alarmone’ (alarm hormone), which conveys the message during alarming situations.

The researchers of the study, led by Prof. Dipanker Chatterji from the Molecular Biophysics Unit, initially observed the structural similarity between Vitamin C and the (p)ppGpp molecule. Biochemistry says that two structurally similar molecules may compete to bind to the same target (enzyme, for example) since binding depends on the molecular structure. In this competition, if one molecule binds to a certain site in the target, the other will not be able to bind since the site is already occupied, thus resulting in one molecule inhibiting the other. Going by this clue, the researchers questioned if vitamin C might inhibit the production of (p)ppGpp by binding to Rel A enzyme - the actual binding target for (p)ppGpp.

The team worked with Mycobacterium smegmatis, a species of bacteria closely related to the infamous M. tuberculosis that causes TB, but is non pathogenic and safe to work with. During the study, the researchers gradually increased the concentration of vitamin C in a solution that contained the bacteria that produced (p)ppGpp. However, at high concentrations of vitamin C, they observed that (p)ppGpp was not being produced and vitamin C completely blocked the synthesis of (p)ppGpp, even inside the bacteria. This blockade is detrimental to bacteria since they need a sustained production of (p)ppGpp during hostile conditions such as nutrient starvation and presence of antibiotics, and for long term survival inside host.

“Vitamin C is known to boost overall immunity in humans since time immemorial. But, its capacity to directly target mycobacteria, specifically its stress response pathway, is a novel concept”, remarks Dr. Kirtimaan Syal, the lead author of the paper.

Many types of bacteria have developed resistance to conventional antibiotic therapy thus evolving into superbugs by a mechanism in which bacterial cells aggregate together to form ‘biofilms’ and give rise to chronic infections. In this study, the researchers have shown that vitamin C reduces the ability of bacteria to form biofilms by as much as 70%.

A previous study has shown that vitamin C, so readily available in the commonest of fruits, can even fight against Multi Drug Resistant (MDR) Tuberculosis and Extensively Drug Resistant (XDR) bacteria, for which currently there is a dearth of effective drugs. Future research on the ability of vitamin C to affect multiple pathways in bacteria may help realize its therapeutic potential. “Perhaps vitamin C, in a chemically modified form, may compensate the requirement for high dosage of Vitamin C that are currently needed in the present study”, remarks Dr. Syal on the future direction of this research.