Biological and Medicinal Chemistry

A Cyclic Di-GMP Network Is Present in Gram-Positive Streptococcus and Gram-Negative Proteus Species


Cyclic di-GMP is a ubiquitous second messenger in bacteria. This work describes the occurrence of a cyclic di-GMP signaling network in Gram-positive Streptococcus species and Gram-negative Proteus. After identification of candidate diguanylate cyclases by homology search in the respective species, the open reading frames were cloned and proteins expressed. Production of cyclic di-GMP was demonstrated by riboswitch assays, detection of cyclic di-GMP in cell lysates by MALDI-FTMS and in cell extracts by standard LC-MS/MS. Expression of the diguanylate cyclases in the heterologous host Salmonella typhimurium showed the expected physiological activity, namely up regulation of biofilm formation and down regulation of motility. The co-localisation of both sole diguanylate cyclases with cellulose or cellulose-like synthases indicates exopolysaccharide biosynthesis to be a conserved trait of cyclic di-GMP signaling.

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