Research / Scientific departments / Structural Biology and Chemistry / Units and Groups / Nuclear Magnetic Resonance of Biomolecules / Research

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 ‘Heme acquisition system’ (Has) we study enables transport of heme (iron protoporphyrin IX) as a source of iron. The Has system can be found in commensal as well as in pathogenic bacteria. For historical reasons, we study the Has system of Serratia marcescens, a Gram-negative, opportunistic pathogen. In the Has system, heme is acquired through an extra-cellular protein HasA called hemophore and an outer membrane receptor HasR. HasA extracts heme from the host’s hemoproteins such as hemoglobin and then delivers it to the HasR receptor. The transport of the heme through HasR and the ejection of the empty HasA are active processes, the energy of which is supplied by the inner membrane HasB complex. HasB is a homologue of a TonB protein, essential for active transportation of nutrients (iron complexes, vitamin B12, nickel) in Gram-negative bacteria.

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.