# Discovery of Novel c-di-GMP-Related Genes in Leptospira interrogans

## TL;DR

This study identifies new genes related to c-di-GMP signaling in Leptospira interrogans, a bacterium that causes leptospirosis, offering insights into its survival and virulence.

## Contribution

The paper reports the discovery of novel c-di-GMP-related genes in Leptospira interrogans through bioinformatics and structural analysis.

## Key findings

- Seventeen proteins with GGDEF domains and others with EAL, HD-GYP, PilZ, and MshEN domains were identified in Leptospira interrogans.
- The findings suggest a complex c-di-GMP signaling network in Leptospira interrogans, potentially involved in biofilm formation and host interactions.
- The study provides a foundation for future functional studies on c-di-GMP's role in Leptospira physiology and virulence.

## 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, a serovar generally associated with severe manifestations of leptospirosis in humans. Our analysis identified seventeen proteins containing GGDEF domain, five proteins containing both GGDEF and EAL domains, four proteins containing EAL domain, five proteins containing HD-GYP domain, twelve 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 signaling 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 roles in physiology, virulence, and persistence.