Sugar-mediated regulation of a c-di-GMP phosphodiesterase in Vibrio cholerae

Biofilm formation protects bacteria from stresses including antibiotics and host immune responses. Carbon sources can modulate biofilm formation and host colonization in Vibrio cholerae, but the underlying mechanisms remain unclear. Here, we show that EIIA^Glc, a component of the phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS), regulates the intracellular concentration of the cyclic dinucleotide c-di-GMP, and thus biofilm formation. The availability of preferred sugars such as glucose affects EIIA^Glc phosphorylation state, which in turn modulates the interaction of EIIA^Glc with a c-di-GMP phosphodiesterase (hereafter referred to as PdeS). In a Drosophila model of V. cholerae infection, sugars in the host diet regulate gut colonization in a manner dependent on the PdeS-EIIA^Glc interaction. Our results shed light into the mechanisms by which some nutrients regulate biofilm formation and host colonization.