Société Française de Biochimie et Biologie Moléculaire

Yoann Santin - January 2019

LISM, CNRS-UMR7255-Marseille In vivo TssA proximity labelling during type VI secretion biogenesis reveals TagA as a protein that stops and holds the sheath Nature Microbiology 3, 1304–1313

Santin, Y.G., Doan, T., Lebrun, R., Espinosa, L., Journet, L., and Cascales, E. (2018)


Yoann Santin, 28 years old, obtained a Bachelor’s degree in cellular biology and a Master's degree in microbiology, plant biology and molecular engineering from the Luminy University (Aix-Marseille). He is currently doing a PhD under the supervision of Dr Eric Cascales at Laboratoire d’Ingénierie des Systèmes Macromoléculaires (Institut de Microbiologie de la Méditerranée). His project is dedicated to the molecular understanding of the structure and mechanism of Type VI secretion systems. These secretion systems can be compared to nano crossbow that deliver toxins, in a contact-dependent manner, directly into eukaryotic or prokaryotic target cells. The work published in Nature Microbiology describes the assembly mechanism of this multi-protein complexes and reveals an additional player in this secretion machine that optimizes its efficiency.


Yoann Santin PhD studentLaboratoire d’Ingénierie des Systèmes Macromoléculaires
Équipe Cascales
CNRS - UMR7255 - 31 chemin Joseph Aiguier
CS 70071 13402 Marseille cedex 09
+33(0)4 91 16 41 56


The type VI secretion system (T6SS) is a multiprotein weapon used by bacteria to destroy competitor cells. The T6SS contractile sheath wraps an effector-loaded syringe that is injected into the target cell. This tail structure assembles onto the baseplate that is docked to the membrane complex. In enteroaggregative Escherichia coli, TssA plays a central role at each stage of the T6SS assembly pathway by stabilizing the baseplate and coordinating the polymerization of the tail. In this study, we adapted an assay based on APEX2-dependent biotinylation to identify the proximity partners of TssA in vivo. By using stage-blocking mutations, we define the temporal contacts of TssA during T6SS biogenesis. This proteomic mapping approach also revealed an additional partner of TssA, TagA. We show that TagA is a cytosolic protein tightly associated with the membrane. Analyses of sheath dynamics further demonstrate that TagA captures the distal end of the sheath to stop its polymerization and to maintain it under the extended conformation.