Toxin-Antitoxin (TA) Systems in Stress Survival and Pathogenesis

Abstract

Mycobacterium tuberculosis (M.tb), by virtue of its ability to evolve, has developed mechanisms that enable it to modulate its growth through regulation of replication, transcription, translation, generation of heterogeneous population of persister cells, etc. for survival in different stressful environment during its infection cycle. Toxin-antitoxin (TA) systems are ubiquitous in prokaryotic genomes that enable them to survive in various unfavourable conditions. A toxin protein may inhibit the growth, whereas an antitoxin may neutralize the effect of toxin in different ways. TA systems are involved in stress adaptation, antimicrobial tolerance or resistance, modification in the physiological state of organisms, biofilms formation, growth regulation for survival, plasmid maintenance, anti-phage activities, virulence, and programmed cell death. Environmental microorganisms express a wider repertoire of TA systems as compared to intracellular human pathogens due to a higher probability to encounter different environmental stresses within their ecosystem. However, the presence of high level of TA systems in M.tb is due to the fact that M.tb has to endure several types of stresses including acidic, hypoxic, oxidative, and immune surveillance within the host for its survival. TA systems are also present in pathogenic bacteria infecting plants. Based on the mechanism of action, different types of TA systems are classified within the microorganisms. Recently, genes related to type II TA systems have been proposed to be useful in genotyping of tuberculosis caused by different strains of M.tb.