New insights into chemical sensing of the human pathogen for cholera
The bacterium Vibrio cholerae is a serious threat to our health because it is the causative agent of cholera. Worldwide, over a billion people per year are at risk of cholera infection. New strains of V. cholerae are resistant to the multiple drugs used to treat cholera, meaning that new types of drugs are needed to fight this disease. Prof. Ariane Briegel (Ultrastructural Biology, IBL) and her colleagues are gaining new insights into the complex chemical sensing system that this pathogen uses to thrive in different environments. They discovered how a new type of receptor actually stabilizes the cytoplasmic arrays of chemical sensing proteins that comprise part of the sensing system. These new insights may open the door to new cholera treatments by targeting key regions of the complex chemical sensing system.
Most motile bacteria, including Vibrio cholerae, possess a highly sensitive and adaptable sensory system that allows the cells to detect changes in nutrient concentrations. They use this ability to navigate towards preferential environments and in some cases facilitate infection of host organisms. This chemosensory system is composed of thousands of chemoreceptor molecules that form highly ordered arrays within the cells. The tips of each receptor are bound with two proteins: a linking protein that supports the array itself and an enzyme that controls the activity of a messenger, which in turn controls the motility apparatus of the cells.
The chemosensory system in Vibrio cholerae is much more complex than that of other well-known bacteria. E. coli for example has only 5 different chemoreceptors, while Vibrio has 43 different receptors encoded in its genome. In addition to a typical membrane-bound chemosensory array, Vibrio cholerae also contains an array that is unbound and purely cytoplasmic. Little is currently known about this unique array.
In order to gain structural and mechanistic insight into this cytoplasmic chemosensory system, Ariane Briegel and colleagues used electron cryo-tomography in combination with fluorescence microscopy, bioinformatics and molecular dynamics flexible fitting methodologies to study its three-dimensional architecture at molecular resolution.
Briegel and her colleagues discovered an unusual architecture: “Instead of interacting with the enzyme and linking protein at a single point, this novel receptor, called DosM, contains two tips that each interact with the protein layer. This means that it can simultaneously bind both protein layers, effectively stabilizing the cytoplasmic arrays.” This is not only the first time a chemoreceptor of such architecture has been described, but: “It is also the first report on the functional role for any chemoreceptor as an array stabilizer.” - says Briegel.
The paper: Cytoplasmic chemotaxis arrays are stabilized by a double signaling-domain chemoreceptor DosM in Vibrio cholera” is published in the Proceedings of the National Academy of Sciences of the United States of America.
