Cross-talk between type three secretion and flagellar assembly in Pseudomonas aeruginosa

Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM), CNRS-IBSM-UPR9027, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France

^* To whom correspondence should be addressed. Email: bleves{at}ibsm.cnrs-mrs.fr.

	Abstract

Pseudomonas aeruginosa cytotoxicity is linked to a type three secretion system (T3SS) that delivers effectors into the host cell. We show here that a negative cross-control exists between T3SS and flagellar assembly. We observed that, in a strain lacking flagella, T3SS gene expression, effector secretion and cytotoxicity were increased. Inversely, we revealed that flagellar gene expression and motility was decreased in a strain overproducing ExsA, the T3SS master regulator. Interestingly, a non-motile strain lacking the flagellar filament (fliC) presented a hyper-efficient T3SS, a non-motile strain assembling flagella (motAB) did not. More intriguingly, a strain lacking motCD genes is a flagellated strain with a slight defect in swimming. However, in this strain, T3SS gene expression was up-regulated. These results suggest that flagellar assembly and/or mobility antagonize T3SS, and that a negative cross-talk exists between these two systems. An illustration of this is the visualization by electron microscopy of T3SS needles in a non-motile P. aeruginosa strain, needles which otherwise are not detected. The molecular basis of the cross-talk is complex and remains to be elucidated, but proteins like MotCD might have a crucial role in signaling between the two processes. In addition, we found that the GacA response regulator affects negatively the T3SS. In a gacA mutant the T3SS effector ExoS is hyper-secreted. Strikingly, GacA was previously reported as a positive regulator for motility. Globally, our data document the idea that some virulence factors are coordinately but inversely regulated depending on the bacterial colonization phase and infection types.