《自然·通讯》论文：铜绿假单胞菌靠 cAMP 与 c-di-GMP 两套互斥信号分工定植表面，附着与扩散两个亚群在气道组织模型中共存
《自然·通讯》11 月 7 日发表 Bruderer、Li、Kaczmarczyk 等作者的论文，解释人类病原体铜绿假单胞菌如何协调在组织表面的定植与毒力：第二信使 cAMP 与 c-di-GMP 在单细胞层面建立互斥的信号状态，通过对四型菌毛的分别控制，生成运动型与表面附着型两个不同亚群。
论文写道，组织表面定植是细菌感染的先决条件，两套信号通路在感染期间如何协调此前并不清楚。研究显示，细菌最初接触表面时 c-di-GMP 升高，激活 FimW，经双极四型菌毛形成实现稳定附着；这一状态随后逐渐被 cAMP 取代，cAMP 使 FimW 依赖的附着失活，并经 FimX 介导菌毛极化，转向表面运动与毒力激活。由此形成的信号转换使两个亚群共存，附着细胞逐渐被扩散细胞取代。
在人体气道组织模型中，研究显示四型菌毛介导的黏附与颤动运动两者都是侵入与组织损伤所必需的。作者据此提出，cAMP 与 c-di-GMP 的相互拮抗信号协调了四型菌毛的互补功能，以优化铜绿假单胞菌的表面定植与感染。论文于 2026 年 2 月 20 日收稿、10 月 19 日接受、11 月 7 日发表。
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.
来源：《自然·通讯》
发布：GSM·美国（发布链接）
图片来源：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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