Séminaire IBS : Molecular adaptation of the membrane complex in bacterial T6SS nanomachine

Par Dr Eric Durand ( Laboratoire de Chimie Bactérienne, Marseille)

The T6SS is dedicated to the delivery of toxin proteins into eukaryotic and prokaryotic cells. T6SS effectors have diverse biochemical activities and can manipulate a wide variety of host cell functions . T6SS is considered as an important virulence factor for a number of human pathogen. The apparent conservation of T6SS composition and architecture conceal the lack of direct investigation of species-specific adaptation. Ground-breaking studies that have described for the first time the architecture of bacterial nanomachines – T1SS, T3SS, T4SS, T6SS – in specific bacteria led their authors to present these structures as an archetypal and universal model of these machineries. However, in depth investigations on these nanomachines in different bacterial species have revealed a highly conserved "core" domain but also significant structural adaptations that have provided valuable information on how these nanomachines work and evolve. In this seminar I will report two specific adaptations of the T6SS « central nervous system », the membrane complex, which is the channel that mediates the transport of toxins across bacterial membranes :
“Flapping of butterfly wings could cause huge waves” : How does the Acinetobacter baumannii membrane complex crosses the outer membrane ? We have characterized for the first time the Ab’s specific T6SS membrane complex (AbMC). Notably, we revealed its unique characteristic and behavior, its membrane localization and assembly dynamics that is coordinated with the sheath dynamics. We also revealed its
original composition, demonstrating that its biogenesis employs three Acinetobacter-specific envelope-associated proteins.
« One small step for man, one giant leap for mankind” : Bacteroides fragilis re-invents the concept of T6SS membrane complex. B. fragilis possesses a functional T6SS albeit with no apparent components building the membrane complex. We have identified five genes in Bacteroides fragilis (tssNQOPR) that are essential for T6SS function and encode a Bacteroidota-specific membrane complex. These genes encode four inner membrane proteins TssN-PQ-O and the outer membrane lipoprotein TssR. We have purified this complex, revealed its dimensions using electron microscopy, and identified a protein-protein interaction network underlying the assembly of the MC including the stoichiometry of the five TssNQOPR components.

Hôte : Cécile Breyton (IBS/Groupe Membrane et pathogènes)