House of cellulose – a new hideout for drug tolerant Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB). The treatment of TB requires administration of multiple drugs for long durations because of the unusual drug tolerance of Mtb. The phenotypic drug tolerance of genetically drug-susceptible Mtb in humans can be explained by its ability to form biofilms. Recent studies from different laboratories suggest that Mtb forms biofilms that harbour drug-tolerant bacteria. These findings have created a new area of research in the field of mycobacterial physiology. Recently, my laboratory has reported that Mtb cells organise themselves into biofilms in response to intracellular thiol reductive stress (Trivedi et al. Nature communications. 2016). Bacteria residing in these biofilms are tolerant towards antimycobacterial drugs. Cellulose is a key component of the extracellular polymeric substances that hold mycobacterial cells together in these biofilms. Here, I discuss the implications of these findings and new hypotheses arising from this study on the biology of Mtb biofilms.

Keywords

• Mycobacterium tuberculosis
• biofilms
• cellulose
• drug tolerance
• thiol reductive stress
• extracellular polymeric substance