Mechanisms of dynamic localization of the bacterial Type 6 secretion system assembly - AimingT6SS

Programme(s): H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)

Topic(s): ERC-2019-COG - ERC Consolidator Grant

Call for proposal: ERC-2019-COG

Funding Scheme: ERC-COG - Consolidator Grant

Grant agreement ID: 865105

Project description:
Bacterial Type 6 secretion system
The Type 6 secretion system (T6SS) allows bacteria to deliver toxins into both eukaryotic and bacterial target cells causing disease or killing competitors. T6SS has several main parts, including a membrane complex, baseplate and long spring-like sheath wrapped around an inner tube. Sheath contraction generates energy to push the tube with toxins through the baseplate and membrane complex out of the cell. Direct contact with the target membrane and precise positioning of T6SS is required for efficient protein translocation. The EU-funded project AimingT6SS will investigate principles of spatial and temporal control of localisation of protein complexes to better understand how it allows bacteria to respond to external cues and interact with the environment. Researchers will study how bacteria sense attacks from other bacteria to dynamically reposition their T6SS. Genetic and biochemical approaches will characterise proteins interacting with the components of T6SS and their role in positioning of T6SS assembly.

Objective:
The Type 6 secretion system (T6SS) allows Gram-negative bacteria to deliver toxins into both eukaryotic and bacterial target cells and thus cause disease or kill competitors. T6SS is composed of four main parts: a membrane complex, a baseplate and a long spring-like sheath wrapped around an inner tube. Sheath contraction generates a large amount of energy to push the tube with associated toxins through the baseplate and membrane complex out of the cell. However, the reach of the T6SS tube is limited and thus a direct contact with the target membrane and precise positioning of T6SS assembly is required for protein translocation. In this proposal, we will unravel principles of spatial and temporal coordination of T6SS assembly that we have recently observed in several bacterial species. We will study how cells sense attacks from neighboring bacteria to dynamically localize its T6SS. We will describe how bacteria initiate and position T6SS assembly in response to physical cell-cell interactions. We will identify the principles and the role of T6SS localization in intracellular pathogens. Using genetic and biochemical approaches, we will identify and characterize proteins interacting with the core components of T6SS and test their role in initiation and positioning of T6SS assembly. We will search for peptidoglycan remodeling enzymes required for T6SS assembly. We will use advanced microscopy techniques to describe dynamic localization of proteins upon T6SS activation to establish the order of their assembly. We will quantify how much T6SS aiming increases efficiency of protein delivery and T6SS function during bacterial competition and pathogenesis. Overall, we will unravel novel principles of spatial and temporal control of localization of protein complexes and show how this allows bacteria to quickly respond to external cues and interact with their environment.