Type II Toxin-Antitoxin Systems in Pseudomonas aeruginosa

Abstract

Toxin-antitoxin (TA) systems are typically composed of a stable toxin and a labile antitoxin; the latter counteracts the toxicity of the former under suitable conditions. TA systems are classified into eight types based on the nature and molecular modes of action of the antitoxin component so far. The 10 pairs of TA systems discovered and experimentally characterised in Pseudomonas aeruginosa are type II TA systems. Type II TA systems have various physiological functions, such as virulence and biofilm formation, protection host against antibiotics, persistence, plasmid maintenance, and prophage production. Here, we review the type II TA systems of P. aeruginosa, focusing on their biological functions and regulatory mechanisms, providing potential applications for the novel drug design.

Keywords: Pseudomonas aeruginosa; biological function; regulatory mechanism; toxin–antitoxin system; type II.

Figure 1

Model of type II toxin–antitoxin systems. The toxin and antitoxin are represented in purple and green, respectively. The antitoxin protein directly interacts with cognate toxin protein and inhibits its toxicity. The labile antitoxin is efficiently degraded when the production of protease, the stable toxin, leads to cell death or growth arrest. The antitoxin and/or toxin–antitoxin (TA) complex can negatively autoregulate the transcription of their operators by recognizing and binding to palindromic sequences.

Figure 2

Biological functions of type II TA systems in P. aeruginosa.

Figure 3

Regulatory pathways of HigB/HigA in control of virulence in P. aeruginosa. HigA negatively regulates the transcription of the TA operon by binding to the palindromic sequence and also negatively regulates the expression of exsA, armZ, and mvfR by binding to their promoter regions. HigB can repress biofilm formation and increase expression of the T3SS genes by negatively regulating the level of c-di-GMP and also negatively regulating motility and pyochelin. ‘→’ indicates induction, and ‘┤’ indicates repression.