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Peer-reviewedCC BY 4.0Applied Microbiology

Quantifying c-di-GMP: A Call for Integration of Biological and Chemical Approaches

Abstract

Bacteria sense, respond, and adapt to rapidly changing environments through highly sensitive intracellular networks. Among them, cyclic-di-GMP (c-di-GMP) is a well-characterized second messenger controlling the transition from planktonic to sessile lifestyles, making it a key determinant of bacterial adaptation and survival. Two main approaches have been developed to investigate c-di-GMP dynamics. The first uses biological biosensors for live-cell monitoring of intracellular c-di-GMP through transcriptional reporters, RNA-based sensors, or protein-based sensors. Their main advantage is real-time, spatiotemporal analysis in living cells, although they generally do not provide absolute quantification. The second approach relies on analytical chemistry, particularly liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), which enables sensitive and accurate quantification of intracellular c-di-GMP across diverse bacterial species. However, the lack of standardized extraction protocols and the need for cell lysis prevent real-time measurements, providing only a snapshot of the total c-di-GMP pool. These approaches are complementary: biosensors reveal dynamic, single-cell responses, whereas LC-MS/MS provides precise global quantification. Nevertheless, most studies rely on only one method, limiting a comprehensive understanding of c-di-GMP biology. Combining both approaches would provide a more integrated view of c-di-GMP signaling and its role in bacterial physiology.

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BibTeX
@article{augias2026quantifying,
  title = {{Quantifying c-di-GMP: A Call for Integration of Biological and Chemical Approaches}},
  author = {Antoine Augias and Charlotte Nirma and Karine Vallée and Sophie Rodrigues and Yvann Bourigault},
  journal = {Applied Microbiology},
  year = {2026},
  month = sep,
  doi = {10.3390/applmicrobiol6090105},
  url = {https://hal.science/hal-05772074v1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Quantifying c-di-GMP: A Call for Integration of Biological and Chemical Approaches
AU  - Antoine Augias
AU  - Charlotte Nirma
AU  - Karine Vallée
AU  - Sophie Rodrigues
AU  - Yvann Bourigault
PY  - 2026
DA  - 2026/09/03
JO  - Applied Microbiology
DO  - 10.3390/applmicrobiol6090105
UR  - https://hal.science/hal-05772074v1
AB  - Bacteria sense, respond, and adapt to rapidly changing environments through highly sensitive intracellular networks. Among them, cyclic-di-GMP (c-di-GMP) is a well-characterized second messenger controlling the transition from planktonic to sessile lifestyles, making it a key determinant of bacterial adaptation and survival. Two main approaches have been developed to investigate c-di-GMP dynamics. The first uses biological biosensors for live-cell monitoring of intracellular c-di-GMP through transcriptional reporters, RNA-based sensors, or protein-based sensors. Their main advantage is real-time, spatiotemporal analysis in living cells, although they generally do not provide absolute quantification. The second approach relies on analytical chemistry, particularly liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), which enables sensitive and accurate quantification of intracellular c-di-GMP across diverse bacterial species. However, the lack of standardized extraction protocols and the need for cell lysis prevent real-time measurements, providing only a snapshot of the total c-di-GMP pool. These approaches are complementary: biosensors reveal dynamic, single-cell responses, whereas LC-MS/MS provides precise global quantification. Nevertheless, most studies rely on only one method, limiting a comprehensive understanding of c-di-GMP biology. Combining both approaches would provide a more integrated view of c-di-GMP signaling and its role in bacterial physiology.
SN  - 2673-8007
ER  -