Tolerance and Persistence to Drugs: A Main Challenge in the Fight Against Mycobacterium tuberculosis

The treatment of tuberculosis is extremely long. One of the reasons why Mycobacterium tuberculosis elimination from the organism takes so long is that in particular environmental conditions it can become tolerant to drugs and/or develop persisters able to survive killing even from very high drug concentrations. Tolerance develops in response to a harsh environment exposure encountered by bacteria during infection, mainly due to the action of the immune system, whereas persistence results from the presence of heterogeneous bacterial populations with different degrees of drug sensitivity, and can be induced by exposure to stress conditions. Here, we review the actual knowledge on the stress response mechanisms enacted by M. tuberculosis during infection, which leads to increased drug tolerance or development of a highly drug-resistant subpopulation.