Mycobacterial response to an acidic environment: protective mechanisms

Given the emergence and spread of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis (Mtb), the world faces the urgency of finding new drugs to combat tuberculosis. Understanding the biochemical/physiological processes enabling Mtb to survive the stressful environment within macrophages and acquire tolerance, resistance and persistence against the stresses are the key to developing new approaches to tackle this health problem. As Mtb gains entry into the respiratory tract and is engulfed by macrophages, lowering pH acts as a primary defence of phagosomes within macrophages and also in the centres of caseating granulomas. It becomes essential for the pathogen to maintain pH homeostasis for survival in these conditions. Acid resistance mechanisms are well known and extensively studied in other bacteria such as Escherichia coli, Lactobacillus spp., Brucella spp., Helicobacter pylori and Listeria monocytogenes. However, in the case of Mtb, acid tolerance and resistance mechanisms still need to be explored in detail. This review aims to describe the current understanding of underlying mechanisms involved in countering low pH faced by Mtb as the acid resistance/tolerance mechanisms contribute to the pathogenesis of the disease. Various strategies for combatting the acidic environment within host macrophages enable mycobacterial pathogens to survive inside the host and may serve as promising targets to control mycobacterial infections.