Bacterial Transmembrane Signalling
(Gisèle Amorim, Alain Chaffotte, Anne Lecroisey, Idir Malki, Ada Prochnicka, Catherine Simenel & Nadia Izadi-Pruneyre)
External stimuli set off signalling cascades in bacteria, which regulate the expression of relevant genes. The presence of certain nutrients like iron complexes generates such a signal detected by an outer membrane receptor. The signal is then transferred across the outer membrane of the bacterium to the cytoplasm where a sigma factor activates the transcription of genes coding for the proteins that allow the acquisition of the nutrient. In some species, this process also regulates the expression of genes associated with the virulence of bacteria improving their adaptation to the host’s environment. The understanding of this kind of signalling at the atomic level opens ways towards therapeutic applications.
The expression of genes coding for the proteins of the Has system is inhibited by intracellular iron and activated by the presence and the bioavailability of heme in the external milieu. This external signal is detected by HasR and propagated via a cascade of molecular interactions of different partners. We have been dissecting various stages of the Has system, in vitro and in vivo, in collaboration with the Unité des Membranes Bactériennes of Institut Pasteur. We solved the 3D structure of several proteins of the Has system, free or bound to their partners. All these structural data as well as the results of in vitro and in vivo experiments performed at different stages of the functioning of the system make it an excellent model for studying signalling in bacteria.