RésuméB. abortus is a pathogen of the cattle responsible for cases of zoonosis from cattle to humans leading to the onset of a chronic disease called brucellosis. The virulence of B. abortus depends on its ability to avoid recognition by the immune system, which includes its ability to invade and thrive within the sentinels of the immune system: the macrophages. The bacterium modulates differents aspect of the host cell biology in order to establish its replicative niche inside the ER of the infected host cell. However, the factors responsible for the establishment as well as the maintenance of the replicative niche are not fully understood, notably at the level of the host cell's biology.
The mitochondrion is an essential organelle for mammalian cell function that has been shown, in recent research, to constitute a prime target for many bacterial pathogens. This involves the modulation of the dynamic aspects of fusion and fission of the mitochondrial network as well as their degradation by specific autophagy (mitophagy) to their advantage.
Previously, our team has shown that B. abortus induces the fragmentation of the
mitochondrial network that appears to be associated with the induction of mitophagy in infected macrophages and epithelial (HeLa) cells. These mitochondrial aspects are accompanied by the activation of a mitophagy axis well described in the literature dependent on the transcription factor HIF-1α and its target gene BNIP-3L/Nix, described as a mitophagy receptor.
The objectives of this master’s thesis were therefore to (i) determine the molecular actors responsible for the stabilisation of HIF-1α in epithelial and myeloid cells infected with B. abortus, (ii) to establish whether there is a link between HIF-1α stabilisation and B. abortusinduced mitochondrial fragmentation and/or mitophagy and (iii) to put these findings into a host-pathogen context.
The major outcome/results of this work revealed a crucial role for iron in the
stabilisation of HIF-1α induced by B. abortus and concludes with encouraging results expanding the role of iron in the occurrence of the mitochondrial fragmentation. If confirmed, these results indicate that the depletion of a metabolite implicated in mitochondrial iron import, derived from the distant evolutionary relationship between Brucella and the mitochondria, is involved in the mitochondrial fragmentation induced by B. abortus.
|la date de réponse||janv. 2022|
|Superviseur||Thierry Arnould (Promoteur) & Xavier De Bolle (Copromoteur)|