Abstract
Toxin-antitoxin (TA) cassettes are encoded widely by bacteria. The modules typically comprise a protein toxin and protein or RNA antitoxin that sequesters the toxin factor. Toxin activation in response to environmental cues or other stresses promotes a dampening of metabolism, most notably protein translation, which permits survival until conditions improve. Emerging evidence also implicates TAs in bacterial pathogenicity. Bacterial persistence involves entry into a transient semi-dormant state in which cells survive unfavorable conditions including killing by antibiotics, which is a significant clinical problem. TA complexes play a fundamental role in inducing persistence by downregulating cellular metabolism. Bacterial biofilms are important in numerous chronic inflammatory and infectious diseases and cause serious therapeutic problems due to their multidrug tolerance and resistance to host immune system actions. Multiple TAs influence biofilm formation through a network of interactions with other factors that mediate biofilm production and maintenance. Moreover, in view of their emerging contributions to bacterial virulence, TAs are potential targets for novel prophylactic and therapeutic approaches that are required urgently in an era of expanding antibiotic resistance. This review summarizes the emerging evidence that implicates TAs in the virulence profiles of a diverse range of key bacterial pathogens that trigger serious human disease.
Highlights
Toxin-Antitoxin ComplexesNatural toxins are molecules produced by a wide variety of organisms—plants, animals and microorganisms
Toxin-antitoxin (TA) cassettes are encoded widely by bacteria
Persistence represents a phenotype exhibited by a small fraction of a bacterial population that temporarily enters a dormant state characterized by reduction of growth rates and metabolic activity
Summary
Natural toxins are molecules produced by a wide variety of organisms—plants, animals and microorganisms. Bacteria express highly potent antibiotics, bacteriocins and other compounds that kill or inhibit growth of other, often closely related, microbial species invading their niche [3] These toxins are not harmful to the microorganisms which produce them. In addition to the preceding toxic factors, most bacterial and archaeal species encode toxin-antitoxin (TA) modules. These systems comprise toxin proteins that disrupt the producing cell’s own molecular processes and cognate antitoxins that block this poisonous activity [4,5,6]. A pair of toxin and antitoxin genes is encoded within a single operon (Figure 1). A pair toxin and antitoxin genes encoded withintoa ensure single operon.
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