Bacterial programmed cell death and toxin-antitoxin system in bacteria

Bacterial programmed cell death (PCD) is a controlled and regulated mechanism of enormous significance in survival, stress adaptation, and biofilm persistence. Bacterial cells actively trigger their death based on internal or external stimuli. This death is not like accidental or passive death (being caused by antibiotics or through lysis, etc.). The toxin-antitoxin (TA) systems are key players in PCD, contributing significantly to antibiotic resistance and bacterial adaptation. The present descriptive review evaluates current literature dealing with the phenomenon of bacterial PCD with particular focus on the molecular biology of Type I and II TA systems (e.g., mazEF, hipBA, hok/sok). Their functions are involved in bacterial stress responses, biofilm growth, and persistence seen in Pseudomonas aeruginosa and Escherichia coli. The TA systems are a combination of toxins that disturb cellular processes (mRNA cleavage, membrane depolarization) and antitoxins that neutralize toxins to modulate PCD. The mazEF TA system blocks protein synthesis, whereas the hok/sok system results in cellular death thereby maintaining plasmid stability. PCD also encourages biofilm formation by eDNA, thereby enhancing antibiotic resistance and structural integrity, which enables bacteria to persist and make infections difficult to treat. Bioinformatic tools and experimental evidence from genetic knock-out and stress response testing studies were combined to clarify the functions of TA systems and regulation under environmental factors. Understanding these mechanisms allows the development of new antibacterial approaches by targeting TA systems to combat antibiotic resistance and reduce persistence. TA systems are redundant; multiple systems with similar mechanisms can synergistically increase persistence, as seen in the deletion of multiple TA loci in E. coli that resulted in reduced persister cell formation. Future studies should explore the interaction between TA systems with other stress-response patterns to develop target intervention mechanisms that can inhibit bacterial survivability without environmental effects.