Year: 2026
Type: article
Abstract: Cyclic di-GMP (bis-(3′ → 5′) cyclic dimeric guanosine monophosphate) is a ubiquitous bacterial second messenger that regulates a wide range of cellular processes, including biofilm formation, motility, virulence, and environmental adaptation. Its intracellular levels are dynamically controlled by diguanylate cyclases (DGCs), which synthesize c-di-GMP from GTP, and phosphodiesterases (PDEs), which degrade it into linear pGpG or GMP. The functional effects of cytoplasmic c-di-GMP are mediated through diverse effector proteins, including PilZ domain-containing receptors, transcription factors, and riboswitches. In Leptospira interrogans, a major pathogenic species responsible for leptospirosis, the regulatory roles of c-di-GMP remain poorly understood. Here, we performed a comprehensive bioinformatics and structural analysis of all predicted c-di-GMP related proteins in L. interrogans serovar Copenhageni strain Fiocruz L1-130. Our analysis identified 17 proteins containing GGDEF domain, five proteins containing both GGDEF and EAL domains, four proteins containing EAL domain, five proteins containing HD-GYP domain, 12 proteins containing PilZ domain, and one protein containing an MshEN domain. Comparative analysis with well-characterized bacterial homologs suggests that L. interrogans possess a complex c-di-GMP network, likely involved in modulating biofilm formation, host-pathogen interactions, and environmental survival. These findings provide new insights into the c-di-GMP regulatory network and on signal transduction in Leptospira and lay the foundation for future functional studies aimed at understanding its role in physiology, virulence and persistence.
Source: Pathogens
Institution: Universidade de São Paulo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,654
Awards: G1198873298, Biology of Bacteria and Bacteriophages Research Center, Muti-user equipment approved in grant 2014/22136-4: isothermal titration calorimeter (ITC) for the determination of thermodynamic parameters of molecular interactions, G2015273503, Protein structural biology applied in the study of c-di-GMP signaling and bacterial secretion systems, G2338360375, G2506544327, G2583628632, G2823776494, G295657101, G3063944240, G3370254160, G3407516606, G3519237112, G5121428398, G6191138830, G6438247056, Comparative genomics of bacterial toxins associated with type IV secretion systems, Design of different fragments of SARS-CoV-2 surface protein spike for the development of fast diagnostic test and vaccine, G8151176212, Understanding the c-di-GMP signaling networks and the Type II secretion system present into the human pathogen Leptospira interrogans Copenhageni, Protein structural biology applied in the study of c-di-GMP signaling and bacterial secretion systems, G8588942737
OpenAlex ID: W7126197666