Toxin-Antitoxin systems: their role in persistence, biofilm formation, and pathogenicity

Abstract

One of the most pertinent recent outcomes of molecular microbiology efforts to understand bacterial behavior is the discovery of a wide range of toxin-antitoxin (TA) systems that are tightly controlling bacterial persistence. While TA systems were originally linked to control over the genetic material, for example plasmid maintenance, it is now clear that they are involved in essential cellular processes like replication, gene expression, and cell wall synthesis. Toxin activity is induced stochastically or after environmental stimuli, resulting in silencing of the above-mentioned biological processes and entry in a dormant state. In this minireview, we highlight the recent developments in research on these intriguing systems with a focus on their role in biofilms and in bacterial virulence. We discuss their potential as targets in antimicrobial drug discovery.

Functional characterization of Aggregatibacter actinomycetemcomitans QSEBC : a bacterial adrengeric receptor and global regulator of virulence.

“…MqsR is the toxin in the mqsRA type II toxin/anti-toxin (TA) system. Type II TA systems are comprised of a labile protein anti-toxin that is co-transcribed in a small operon with its cognate protein toxin [81]. Under normal conditions, the anti-toxin binds to the toxin to negate its effects.…”

“…TA systems can be activated by the Lon [82] or Clp [83] proteases which more readily degrades the labile anti-toxin, releasing the toxin [85,83]. Most toxins act as endoribonucleases [84], but some toxins can target other factors such as DNA gyrase, elongation factors, or uridine diphosphate-Nacetylglucosamine [81]. TA systems are activated by a signaling mechanism involving RelA/SpoT, the signaling nucleotide (p)ppGpp, and polyphosphate (PolyP) [85].…”

“…A. actinomycetemcomitans contains both the Lon (D11S_1522) and Clp (D11S_2042-2043) proteases. The activation of TA systems through this signaling mechanism is hypothesized to be a way for the bacterium to form a persister state in response to stress [81,84]. TA systems can respond to a variety of stressors, and they can be functionally redundant.…”

“…They comprise an anti-toxin that is co-transcribed with its cognate toxin [81]. In type II TA systems, both the toxin and the anti-toxin are proteins with the anti-toxin being more labile and therefore more easily degraded by proteases such as Clp [83] and Lon [82].…”

“…Many anti-toxins also bind to their own promoter to auto-regulate expression of the operon. Toxin activity can vary but most toxins function as either ribosome dependent or independent mRNA endoribonucleases that cleave mRNA at certain specific sequences [81,109,110]. Some cleave mRNA promiscuously such as the RelE of E.coli which cleaves between the second and third position of an upstream purine [111].…”