Toxin-antitoxin systems in bacterial pathogenesis

Abstract

Toxin-Antitoxin (TA) systems are abundant in prokaryotes and play an important role in various biological processes such as plasmid maintenance, phage inhibition, stress response, biofilm formation, and dormant persister cell generation. TA loci are abundant in pathogenic intracellular micro-organisms and help in their adaptation to the harsh host environment such as nutrient deprivation, oxidation, immune response, and antimicrobials. Several studies have reported the involvement of TA loci in establishing successful infection, intracellular survival, better colonization, adaptation to host stresses, and chronic infection. Overall, the TA loci play a crucial role in bacterial virulence and pathogenesis. Nonetheless, there are some controversies about the role of TA system in stress response, biofilm and persister formation. In this review, we describe the role of the TA systems in bacterial virulence. We discuss the important features of each type of TA system and the recent discoveries identifying key contributions of TA loci in bacterial pathogenesis.

Keywords: Biofilm formation; Host stress; Infection; Intracellular survival; Toxin-antitoxin; Virulence.

Fig. 1

Types of TA system- TA system has been categorized in eight types based on the antitoxin mode of inhibition of toxin. A. In type I, antitoxin RNA binds to toxin mRNA and inhibits toxin mRNA translation. B. In type II, antitoxin interacts with toxin and inhibits toxin activity. C. In type III, antitoxin RNA binds to toxin and inhibits its activity. D. In type IV antitoxin binds to the substrate of toxin and inhibits toxin activity indirectly. E. In type V, antitoxin cleaves toxin mRNA and inhibits its translation. F. In type VI, antitoxin interacts with toxin and act as proteolytic adapter for degradation for toxin. G. In type VII, antitoxin interacts with toxin and inhibits toxin activity via post-translational modification. H. In type VIII, antitoxin RNA inhibits the transcription of toxin or promotes toxin RNA degradation. Toxins of all types of TA system are either bacteriostatic or bactericidal in nature.

Fig. 2

Contribution of TA systems in bacterial pathogenesis. During infection, bacteria get exposed to host stresses such as nutrient deprivation, oxidation, immune response and antimicrobials. Induction of toxins helps bacteria to establish successful infection, adapt host environment, intracellular survival and fitness, host cell lysis, and better colonization in organs. Toxins increase biofilm formation and persister cell formation which assist choronic and persistant infection. TA loci reprogramme the metabolic genes to adapt the host stesses and enhance bacterial virulence.