- That vitamin C, an anti-oxidant agent, boosts and strengthens immunity is well known.
- Its ability to speed-up recovery from tuberculosis and impede the TB causing bacteria from causing disease, and even kill the bacteria in culture at high concentration are also known.
- Now, a study by a team of researchers at the Indian Institute of Science (IISc), Bengaluru has found the molecular mechanism by which vitamin C impedes and even kills Mycobacterium smegmatis, a non-pathogenic bacterium that belongs to the same genus as the TB-causing mycobacteria.
- During times of stress or hostile conditions, such as increased temperature and presence of antibiotics, bacteria tend to come together and form a biofilm to protect themselves. The stress response pathway is crucial for bacteria to survive during hostile conditions. So blocking this pathway is a sure way of killing the bacteria.
- In mycobacterium, the (p)ppGpp (Guanosine pentaphospahte or Guanosine tetraphosphate) is a key molecule in the stress response pathway. The (p)ppGpp is synthesised by Rel protein, which in turn is made by the Rel gene.
- The team led by Dipankar Chatterji from the Molecular Biophysics Unit at IISc looked at the effects of vitamin C on the stress response pathway. “We chose vitamin C because its structure is similar to (p)ppGpp,” says Prof. Chatterji. “So we hypothesised that vitamin C should be competing to bind to the Rel enzyme and inhibiting (p)ppGpp synthesis.”
- To test their hypothesis, the researchers conducted experiments using M. smegmatis. M. smegmatis is used as a model organism for TB-causing Mycobacterium tuberculosis.
Role of vitamin C
- In vitro studies showed “significant” inhibition of (p)ppGpp synthesis in the presence of vitamin C. The inhibition level was seen to increase as the vitamin C concentration increased. The more the vitamin C concentration, the greater the possibility of vitamin C binding to the Rel enzyme, thus inhibiting (p)ppGpp synthesis. At about 10 mM concentration, the synthesis of (p)ppGpp molecule was completely inhibited.
- The binding of vitamin C to the Rel enzyme is weak and this explains why high concentration of vitamin C is needed to inhibit (p)ppGpp synthesis.
- “Using Mycobacterial cells we found that 1 mM of vitamin C produced 50% inhibition in (p)ppGpp synthesis. Vitamin C is able to get inside cells and inhibit (p)ppGpp synthesis,” says Kirtimaan Syal from IISc, the first author of the paper.
- When 2 mM of vitamin C was added, “significant” defect in biofilm formation was seen. There was more than 50% reduction in viability of cells in a matter of four days when M. smegmatis was treated with 2mM of vitamin C. The viability of cells reduced even further with time, raising the possibility of therapeutic implications.
- “This suggests that vitamin C can act as a precursor for more potential inhibitors; it can be chemically modiﬁed into more potential derivatives,” .
- “Vitamin C is natural, and it can form one of the nutrient-based treatments of the disease.
- Vitamin C is water soluble and has no toxic effect,”.
Source: The Hindu