Pseudomonas aeruginosa: cAMP and c-di-GMP set exclusive cell states in a human airway tissue model
Researchers in Basel and Lausanne found that two second messengers split P. aeruginosa cells into attached and motile subpopulations; both functions were needed for invasion in a tissue model.
A team from the Biozentrum at the University of Basel, together with colleagues from EPFL Lausanne and University Hospital Basel, has described in Nature Communications how two second messengers, cAMP and c-di-GMP, coordinate surface behaviour and virulence in the human pathogen Pseudomonas aeruginosa. Colonisation of host tissue surfaces is a prerequisite for bacterial infection, but it had remained unclear how these two pathways are coordinated during tissue infection. The authors report that cAMP and c-di-GMP establish mutually exclusive signalling states at the single-cell level. nature.com
Nature Communicationsnature.comOpen source ↗
Two signalling states and type IV pili
According to the authors, the pathways act through type IV pili (T4P) in a pathway-specific way and generate distinct subpopulations of motile and surface-attached cells. Initial surface contact triggers an increase in c-di-GMP. This activates FimW and drives stable attachment through the formation of bipolar T4P.
Over time this state is progressively replaced by cAMP. The messenger inactivates FimW-dependent attachment and induces FimX-mediated T4P polarisation, surface motility and activation of virulence. The transition enforces coexisting subpopulations, in which attached cells are gradually displaced by spreading cells. Thus the same pili serve anchoring or movement, depending on which messenger dominates.
Tests in a human airway tissue model
The team then used a human airway tissue model. In it, both T4P-mediated adhesion and twitching motility were required for invasion and tissue damage. nature.com
Nature Communicationsnature.comOpen source ↗ Based on this, the authors propose that reciprocal cAMP–c-di-GMP signalling coordinates complementary T4P functions and so optimises surface colonisation and infection by P. aeruginosa.
The first authors, Maya Bruderer and Jiangning Li, contributed equally; the correspondence authors are Benoit-Joseph Laventie and Urs Jenal. The data come from a tissue model, not from patients.
