An in vivo inducible gene of Pseudomonas aeruginosa encodes an anti‐ExsA to suppress the type III secretion system

Abstract

SummaryWe have previously reported on the isolation of in vivo inducible genes of Pseudomonas aeruginosa using IVET system. One of such genes isolated from burn mouse infection model encodes a short open reading frame with unknown function. In this study, we demonstrate that this gene product specifically suppresses the expression of type III secretion genes in P. aeruginosa , thus named PtrA (Pseudomonas type III repressor A). A direct interaction between the PtrA and type III transcriptional activator ExsA was demonstrated, suggesting that its repressor function is probably realized through inhibition of the ExsA protein function. Indeed, an elevated expression of the exsA compensates the repressor effect of the PtrA. Interestingly, expression of the ptrA is highly and specifically induced by copper cation. A copperresponsive two-component regulatory system, copRcopS , has also been identified and shown to be essential for the copper resistance in P. aeruginosa as well as the activation of ptrA in response to the copper signal. Elevated expression of the ptrA during the infection of mouse burn wound suggests that P. aeruginosa has evolved tight regulatory systems to shut down energy-expensive type III secretion apparatus in response to specific environmental signals, such as copper stress.

High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system: implications for tryptophan catabolites

“…This process represents the positive activation loop of the T3SS that is triggered by cell contact in vivo and can be mimicked by calcium depletion in vitro. Besides this major regulatory operon, other factors regulate T3SS expression, including cyclic AMP with Vfr, the Pseudomonas catabolite repression homologue (Wolfgang et al, 2003), PtrA (Ha et al, 2004) and the RetS/LadS/GacAS two-component regulatory systems (Goodman et al, 2004;Laskowski et al, 2004;Ventre et al, 2006;Zolfaghar et al, 2005). Taken together, these published data indicate that P. aeruginosa uses a complex set of signalling pathways both to activate and to repress T3SS expression in response to extracellular and intracellular triggers (Yahr & Wolfgang, 2006).…”

PtrB of Pseudomonas aeruginosa Suppresses the Type III Secretion System under the Stress of DNA Damage

“…Expression of this gene is specifically inducible by high copper signal in vitro through a CopR/S two-component regulatory system, suggesting an important in vivo signal during infection of burn mouse skin tissue (17,36). Also, we have shown that mutation in a mucA gene not only activates alginate production but also represses the expression of the TTSS (50).…”

“…Recently, we have demonstrated that a gene highly inducible during infection of the burn mouse model, designated ptrA, encodes a small protein which inhibits TTSS through direct binding to ExsA and thus functions as an anti-ExsA factor (17). Expression of this gene is specifically inducible by high copper signal in vitro through a CopR/S two-component regulatory system, suggesting an important in vivo signal during infection of burn mouse skin tissue (17,36).…”

The Copper-Inducible cin Operon Encodes an Unusual Methionine-Rich Azurin-Like Protein and a Pre-Q 0 Reductase in Pseudomonas putida KT2440

“…cop boxes are found in promoters preceding P. syringae copA (24) and E. coli cusC (10) and pcoA (26). For P. aeruginosa, PA2808 (ptrA), which precedes cinA, has been reported to be induced by copper (14, 36) via a mechanism involving the two-component system cinRS (PA2809 and PA2810) and resulting in the repression of the type III secretion system (14).…”