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Updated: Aug 5, 2026
11:31
Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa
Published on: June 30, 2016
The Cyclic Di-GMP Receptor HpoR Modulates Mycobacterial Multidrug Susceptibility by Regulating IniBAC-Mediated
Xiao Liu1,2, Xiaocui Ling1,2, Kun Wang1
1State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi Technology Innovation Center for Microbial Resources Development and Utilization, College of Life Science and Technology, Guangxi University, Nanning 530004, China.
Microorganisms
|July 28, 2026
Summary
Cyclic di-GMP (c-di-GMP) reduces isoniazid (INH) susceptibility by interacting with the HpoR receptor. This interaction modulates the iniBAC operon, decreasing envelope permeability and INH resistance in mycobacteria.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Discovery
Background:
- Isoniazid (INH) is a key antimycobacterial drug targeting cell wall biosynthesis.
- Understanding drug resistance mechanisms, particularly INH tolerance, is crucial for combating pathogenic mycobacteria.
- The iniBAC operon is known to influence INH tolerance and envelope permeability, but its transcriptional regulation under INH stress is not fully understood.
Purpose of the Study:
- To investigate the role of the second messenger cyclic di-GMP (c-di-GMP) in modulating INH susceptibility in mycobacteria.
- To identify the downstream receptor(s) and regulatory pathways of c-di-GMP in mycobacterial drug response.
- To elucidate the mechanism by which c-di-GMP affects the iniBAC operon and subsequent drug susceptibility.
Main Methods:
- Investigated the effect of c-di-GMP on INH susceptibility in *M. bovis* BCG and *M. smegmatis*.
- Identified HpoR as the c-di-GMP receptor involved in INH tolerance.
- Analyzed the transcriptional regulation of the iniBAC operon by c-di-GMP and HpoR using concentration-dependent assays.
Main Results:
- Demonstrated that c-di-GMP significantly reduces INH susceptibility in mycobacteria.
- Showed that c-di-GMP acts through the receptor HpoR to alleviate repression of the iniBAC operon.
- Observed a concentration-dependent decrease in envelope permeability and modulation of multidrug susceptibility due to c-di-GMP/HpoR interaction.
Conclusions:
- c-di-GMP, via the HpoR receptor, plays a critical role in regulating INH susceptibility in mycobacteria.
- The c-di-GMP-HpoR-iniBAC regulatory axis offers a novel target for understanding and potentially overcoming INH resistance.
- This regulatory mechanism is likely conserved across pathogenic mycobacterial species, highlighting its importance in intrinsic drug resistance.
Keywords:
c-di-GMPenvelope permeabilitymultidrug susceptibilitymycobacteriatranscriptional regulationMore Related Videos
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