Philippe Leone’s group

Bacterial secretion system and nematode innate immunity.


Type IX Secretion System (T9SS)

T9SS KLMN core complex

The T9SS is responsible for Porphyromonas gingivalis pathogenesis through secretion of virulence factors, and for Flavobacterium johnsoniae motility through secretion of adhesins. Among the 18 identified proteins that are involved in T9SS function, the K-L-M-N proteins are supposed to form the core complex. We propose that the outer membrane ring-shaped K-N complex serves as an interaction platform to recruit the inner membrane L-M complex, and that the L-M complex is a novel rotary motor driven by proton motive force. Our objective is to solve the structures of the isolated soluble domains of L and N proteins, and of the L-M and K-L-M-N membrane complexes from the two bacterial models, by X-ray crystallography and cryo-EM (in collaboration with Olivier Lambert, ICBMN, Bordeaux). The function of the L-M complex, and notably its role as a rotary motor, will be addressed by in vivo approaches (in collaboration with Eric Cascales, LISM, Marseille).

C. elegans innate immunity

This project, in collaboration with Jonathan Ewbank (CIML, Marseille), aims at deciphering the host-pathogen relationships between C. elegans and the obligate fungal pathogen Drechmeria coniospora. By RNAi screening on whole C. elegans genome, our collaborators identified 270 genes involved in the nematode innate immunity. Among them, only 33 have no functional annotation, and even fewer are specific to nematodes and are not present in other metazoans. On the other hand, virulence factors from D. coniospora were identified and those not present in other fungi and without functional annotation were selected. Our objective is to solve the structures of the nematode and D. coniospora specific proteins; functional studies are carried out in parallel by our collaborators.



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