biostudies-literatureUnknown171(2)Bagchi SCyclic-di-guanosine monophosphate (c-di-GMP) plays an important role in bacterial signalling networks. C-di-GMP exerts a regulatory function through binding to diverse molecules that include transcription factors, riboswitches and sensor kinases (SKs), thereby regulating diverse processes. Here, we demonstrate the crosstalk between c-di-GMP and the SK MtrB of <i>Mycobacterium tuberculosis</i>. MtrB phosphorylates and regulates its cognate response regulator MtrA. C-di-GMP binds directly to the cytosolic domain of MtrB to inhibit its autophosphorylation. C-di-GMP levels in <i>M. tuberculosis</i> were manipulated by overexpressing a c-di-GMP synthesizing enzyme <i>ydeH</i> and a degrading enzyme <i>rv1357c</i>. We demonstrate that overexpression of <i>ydeH</i> lowers growth of the bacterium Microbiology (Reading, England)https://www.ebi.ac.uk/biostudies/studies/S-EPMC12282275biostudies-literatureCrosstalk between cyclic-di-guanosine monophosphate and the sensor kinase MtrB regulates MtrA-dependent genes, bacterial growth, biofilm formation and lysosomal trafficking of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;.PMC12282275Mal SKundu MBasu JSharma AKBagchi SfalseCrosstalk between cyclic-di-guanosine monophosphate and the sensor kinase MtrB regulates MtrA-dependent genes, bacterial growth, biofilm formation and lysosomal trafficking of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;.Cyclic-di-guanosine monophosphate (c-di-GMP) plays an important role in bacterial signalling networks. C-di-GMP exerts a regulatory function through binding to diverse molecules that include transcription factors, riboswitches and sensor kinases (SKs), thereby regulating diverse processes. Here, we demonstrate the crosstalk between c-di-GMP and the SK MtrB of <i>Mycobacterium tuberculosis</i>. MtrB phosphorylates and regulates its cognate response regulator MtrA. C-di-GMP binds directly to the cytosolic domain of MtrB to inhibit its autophosphorylation. C-di-GMP levels in <i>M. tuberculosis</i> were manipulated by overexpressing a c-di-GMP synthesizing enzyme <i>ydeH</i> and a degrading enzyme <i>rv1357c</i>. We demonstrate that overexpression of <i>ydeH</i> lowers growth of the bacterium 2025-01-01T00:00:00Z2025 Feb2026-03-31T10:42:32.277Z2025-08-24T03:08:52.301ZS-EPMC122822753991898710.1099/mic.0.001532