A complex two-component system CdgKA-CdgSH fine-tunes c-di-GMP homeostasis in a Cyanobacterium
- 1Institute of Hydrobiology, Chinese Academy of Sciences
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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BibTeX
@misc{sun2026complex,
title = {{A complex two-component system CdgKA-CdgSH fine-tunes c-di-GMP homeostasis in a Cyanobacterium}},
author = {Q.-X. Sun and Z.-R. Ding and C.-C. Zhang and X. Zeng},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.750938},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.750938v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A complex two-component system CdgKA-CdgSH fine-tunes c-di-GMP homeostasis in a Cyanobacterium
AU - Q.-X. Sun
AU - Z.-R. Ding
AU - C.-C. Zhang
AU - X. Zeng
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.750938
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.750938v1
AB - 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.
ER -