Bacterial toxin-antitoxin modules: classification, functions, and association with persistence

Toxin-antitoxin (TA) modules are ubiquitous gene loci among bacteria and are comprised of a toxin part and its cognate antitoxin part. Under normal physiological conditions, antitoxin counteracts the toxicity of the toxin whereas, during stress conditions, TA modules play a crucial role in bacterial physiology through involvement in the post-segregational killing, abortive infection, biofilms, and persister cell formation. Most of the toxins are proteinaceous that affect translation or DNA replication, although some other intracellular molecular targets have also been described. While antitoxins may be a protein or RNA, that generally neutralizes its cognate toxin by direct interaction or with the help of other signaling elements and thus helps in the TA module regulation. In this review, we have discussed the current state of the multifaceted TA (type I-VIII) modules by highlighting their classification and specific targets. We have also discussed the presence of TA modules in the various pathogens and their role in antibiotic persistence development as well as biofilm formation, by influencing the different cellular processes. In the end, assembling knowledge about ubiquitous TA systems from pathogenic bacteria facilitated us to propose multiple novel antibacterial strategies involving artificial activation of TA modules.