A unifying theme across bacterial species is that biofilm formation coincides with the synthesis of the cellular signaling molecule c-di-GMP . The correlation between high c-di-GMP concentration in the cell and biofilm formation or low c-di-GMP levels and motility has been demonstrated in several bacterial species, e.g. Escherichia coli, Pseudomonas aeruginosa, and Salmonella enterica and this feature seems to be conserved in Leptospira. Our current work shows that the c-di-GMP regulation pathway is a regulatory network involved in biofilm formation, virulence and motility in the pathogen Leptospira interrogans. We hypothesize that pathogenic Leptospira utilize c-di-GMP signaling and tightly control its regulation, wavering from high level during the environmental phase, promoting biofilm formation to favor resistance, to low level once infecting the mammalian host, allowing the bacteria to disseminate from the subcutaneous site and cause systemic infection.
This project aims at determining the contribution of the signaling nucleotide c-di-GMP to biofilm formation in Leptospira interrogans . We propose to clarify the regulation of Leptospira biofilm formation by investigating the underlying genetic control network regulated by c-di-GMP. We will address the above research question using comparative transcriptomics methods.