An armour protects and primes TB bacteria against an antibiotic

– Sunreeta Bhattacharya (with inputs from authors)

The bacterium that causes tuberculosis (TB) is notorious for gaining resistance to antibiotics, which makes the treatment of the disease difficult.

A new study by P Ajit Kumar and colleagues from the Department of Microbiology and Cell Biology shows that when TB bacteria encounter the common anti-TB drug, rifampicin, a small proportion of the bacterial cells develop a thick, armour-like capsule. This armour reduces the entry of the drug, thereby preventing the build-up of lethal levels of it within the cells. This strategy ensures the survival of these cells despite the continued presence of lethal levels of the drug outside.

The team also discovered that this capsule consists of certain types of carbohydrate molecules that make it difficult for rifampicin to enter the cells. The small amount of rifampicin that manages to enter the cells triggers a stress reaction, which in turn causes mutations in the bacterial DNA. In the subsequent generations, those bacterial cells that have gained rifampicin-resistant mutations escape the antibiotic-mediated death. These mutant bacteria grow and divide to generate new populations of cells that are entirely rifampicin-resistant and hence survive in the presence of lethal doses of the drug.

This finding unveils one of the mechanisms that TB bacteria use to protect themselves and survive against the anti-TB drug, rifampicin. It can aid in the identification of novel drug targets to design drugs that can prevent the formation of this armour, and therefore prevent the emergence of rifampicin-resistant bacteria. This would make the TB treatment regimen effective.

REFERENCE:

Sebastian, J, Nair, RR, Swaminath, S and Ajitkumar, P, Mycobacterium tuberculosis Cells Surviving in the Continued Presence of Bactericidal Concentrations of Rifampicin in vitro Develop Negatively Charged Thickened Capsular Outer Layer That Restricts Permeability to the Antibiotic, Frontiers in Microbiology, 2020, 11 (3262).

https://doi.org/10.3389/fmicb.2020.554795

LAB WEBSITE:

https://mcbl.iisc.ac.in/p-ajitkumar/