Signals Modulating Cyclic di-GMP Pathways in Vibrio cholerae

Abstract

Vibrio cholerae is an aquatic bacterium that is also the causative agent of the diarrheal disease cholera. In this bacterium, the secondary messenger, cyclic di-GMP, regulates the lifestyle transition between a motile state and a sessile biofilm state as well as other key processes such as virulence factor production. The V. cholerae genome encodes 62 proteins that contain GGDEF, EAL, or HD-GYP domains that are predicted to be involved in the synthesis or degradation of cyclic di-GMP. Presumably, one or more signals modulate the activity of each of these proteins to regulate cyclic di-GMP levels in the cell; however, to date, only a few of these signals have been elucidated. In this chapter, we present our current knowledge about the signals that have an effect on cyclic di-GMP signaling in V. cholerae and the signaling networks that play direct or indirect roles in processing these signals. These signals include polyamines, bile acids, temperature, and molecular oxygen. We also discuss how cyclic di-GMP signaling networks interact with other signal transduction pathways, such as quorum sensing, to regulate behavior. In addition to the many unidentified signals, there are other gaps in our knowledge including how signal specificity and processing is achieved and what is the nature and the extent of crosstalk among cyclic di-GMP and other signal transduction networks. Future research addressing these questions will help us better understand how V. cholerae assimilates cues in both aquatic habitats and host organisms to optimize its response to specific environments through cyclic di-GMP signaling.