Nature Communications Paper: Antagonistic cAMP and c-di-GMP Signalling Coordinates Pseudomonas aeruginosa Surface Colonization, Splitting Cells Into Attached and Spreading Subpopulations

A paper published in Nature Communications on November 7 by Bruderer, Li, Kaczmarczyk and colleagues explains how the human pathogen Pseudomonas aeruginosa coordinates surface colonization and virulence: the second messengers cAMP and c-di-GMP establish mutually exclusive signalling states at the single-cell level, generating distinct subpopulations of motile and surface-attached cells through pathway-specific control of type IV pili.
The authors write that efficient colonisation of host tissue surfaces is a prerequisite for bacterial infection, and how the two pathways are coordinated during tissue infection had remained unclear. They show that initial surface contact triggers an increase in c-di-GMP, activating FimW and driving stable attachment via bipolar type IV pili formation. That state is progressively replaced by cAMP, which inactivates FimW-dependent attachment and induces FimX-mediated pilus polarisation, surface motility and virulence activation. The resulting transition enforces coexisting subpopulations, with attached cells gradually displaced by spreading cells.
Using a human airway tissue model, the authors show that both pilus-mediated adhesion and twitching motility are required for invasion and tissue damage. On that basis they propose that reciprocal cAMP–c-di-GMP signalling coordinates complementary type IV pili functions to optimise surface colonisation and infection. The paper was received on February 20, 2026, accepted on October 19, 2026 and published on November 7, 2026.
Source: Nature Communications
Published by GSM · USA (original Chinese edition)
Photo: 图:铜绿假单胞菌扫描电镜图。Janice Haney Carr 摄,美国疾控中心(CDC),Wikimedia Commons,公共领域。 / Photo: Scanning electron micrograph of Pseudomonas aeruginosa. Photo by Janice Haney Carr, CDC, Wikimedia Commons, public domain.
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