Toxin–Antitoxin Systems and their Role in Maintaining the Pathogenic Potential of Causative Agents of Sapronoses

In interepidemic periods, causative agents of sapronoses typically employ a variety of mechanisms for maintaining the viability in terrestrial parasitic systems, associated with different adaptive strategies and utilized by their populations to survive. Unlike spore-forming bacteria, causative agents of sapronoses form resistant cell forms: viable but nonculturable (VBNC) cells and persistence (dormant) cells. The implementation of these strategies is mediated by the influence of various stressors of the environment and is characterized by a decrease in metabolism, a change in the morphology and physiology of the bacterial cell, and also the cessation of its replication. While most of the bacterial population is killed under antibiotic exposure, this fraction of pathogens transiently exhibits a phenotypic multidrug-tolerance, causing relapses and chronic courses of many sapronoses. It is important to note that when these resistant cell forms retain virulence and when favorable conditions occur, they are again transformed into active vegetative forms. For this reason, understanding mechanisms, allowing a fraction of the bacterial population to acquire transiently multidrug-tolerance represents an essential step to eradicate these dormant populations. The discovery of the genetic modules of bacterial toxin-antitoxin systems (TAS) in recent years, was proposed to be an ideal and promising candidate to control these complex regulatory molecular mechanisms. Overexpression of the toxins often increases persister frequency in a defined population. In this review, we summarize the scientific data regarding the TAS modules involved in bacterial persistence to be used as antibiotics for the conservation of the pathogenic potential of resistant forms of pathogens of natural focal sapronosis in interepidemic periods.