A complex two-component system CdgKA-CdgSHA fine-tunes c-di-GMP homeostasis in a Cyanobacterium
Year: 2026
Type: preprint
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. Importance Cyanobacteria are photosynthetic microbes being developed for sustainable fuel and chemical production, but their growth efficiency depends on maintaining an appropriate cell size. This study identifies a molecular pathway with CdgKA-CdgSHA in a cyanobacterium that controls cell size and growth by the key signaling molecule c-di-GMP. This pathway controls c-di-GMP degradation, while a previously identified CdgK-CdgS signaling system controls c-di-GMP synthesis. These systems together fine-tune c-di-GMP homeostasis in response to environmental conditions. This work provides a foundation for engineering cyanobacteria with improved growth characteristics for industrial applications.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7212853247