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bioRxiv · 10.64898/2026.09.11.750938

A complex two-component system CdgKA-CdgSH fine-tunes c-di-GMP homeostasis in a Cyanobacterium

Sun, Q.-X.·Ding, Z.-R.·Zhang, C.-C.·Zeng, X.
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Abstract

The second messenger c-di-GMP plays a critical role in regulating cell size and growth in the cyanobacterium Anabaena sp. PCC 7120. While all 16 c-di-GMP metabolic enzymes and the primary receptor CdgR have been identified, how metabolic enzyme activity is controlled to maintain c-di-GMP homeostasis remains largely unexplored. Here, using a suppressor-screening approach based on c-di-GMP-deficient mutants, we identify All0729 (CdgKA) as a regulator that orchestrates c-di-GMP homeostasis and cell size regulation. Genetic and quantitative analyses demonstrate that CdgKA acts upstream of All2306 (CdgSHA), the reported major c-di-GMP hydrolase, to modulate the activity of the latter. While c-di-GMP synthesis mutants displayed reduced c-di-GMP levels and decreased cell size, inactivation of cdgKA or cdgSHA in these mutant backgrounds rescued both the c-di-GMP levels and cell size. We propose that CdgKA and CdgSHA form a complex two-component system, and the phosphorylation of CdgSHA enhances its c-di-GMP-degrading activity. While the previously identified two-component system composed of CdgK-CdgS regulates c-di-GMP synthesis, the CdgKA-CdgSHA system controls its degradation. Together, they constitute a dual TCS network that precisely tunes c-di-GMP levels and cell size, establishing a regulatory link between two-component signaling and second messenger homeostasis in cyanobacteria.

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Sun, Q.-X., Ding, Z.-R., Zhang, C.-C., Zeng, X.. 2026-09-13. A complex two-component system CdgKA-CdgSH fine-tunes c-di-GMP homeostasis in a Cyanobacterium. https://doi.org/10.64898/2026.09.11.750938

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