5th de Duve Lecture: Watch the podcast!
Pascale Cossart enlightens us on the molecular and cellular bases of bacterial infections.
The molecular virology (VIRO) team of Thomas Michiels published, in the prestigious journal PNAS, a striking observation originally made by Frédéric Sorgeloos and Michael Peeters. Unrelated microbes, including some RNA viruses, DNA viruses and bacteria produce proteins, which hijack a family of cellular enzymes named "RSKs" to their own benefit. Remarkably, these pathogens evolved in a convergent fashion to hijack the cellular enzymes through the very same mechanism.
This work not only unravels a novel mechanism involved in pathogenesis but also paves the way to the identification of additional pathogens, which make use of the same strategy. This work also suggests novel therapeutic approaches to dampen the virulence of such microbes.
The "model of the clamp" proposed in this article proposes that proteins produced by various microbes recruit and force the contact between a cellular enzyme whose activity is to phosphorylate proteins and a cellular substrate for this enzyme. Once phosphorylated, the substrate would act to inhibit the immune response of the host and to promote the infection.
A case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif
Sorgeloos F, Peeters M, Hayashi Y, Borghese F, Capelli N, Drappier M, Cesaro T, Colau D, Stroobant V, Vertommen D, de Bodt G, Messe S, Forné I, Mueller-Planitz F, Collet JF, and Michiels T
PNAS (2022) 119(5): e2114647119
This study has been supported by EOS (ID 30981113), IAP (IAP-P7/45), FNRS ([PDR] T.0185.14, [CDR] J.0143.18F) and Fonds Maurange.