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ESX-4 T7SS SIGNED

Structure/function of a prototypic type VII secretion system from a fast-growing pathogenic mycobacteria

Total Cost €

0

EC-Contrib. €

0

Partnership

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 ESX-4 T7SS project word cloud

Explore the words cloud of the ESX-4 T7SS project. It provides you a very rough idea of what is the project "ESX-4 T7SS" about.

genetics    awaited    microbiology    resolution    mediated    eccd    components    ecce4    survive    inactive    tuberculosis    questions    structural    intracellular    virulence    date    structure    abscessus    cell    membrane    secretion    interdisciplinary    host    rgm    functional    eccc    deemed    esx    infections    experiments    t7ss    sgm    collaborators    multiply    intact    crosses    infection    substrate    shown    survival    diverse    inner    esx4    lack    responsible    function    mab    acquired    combine    form    lab    investigation    modeling    clinically    integrative    opportunistic    characterization    central    rendering    experimental    resistant    possess    functionally    multiple    data    mechanism    active    macrophages    mycobacterium    mycobacteria    except    tuberculous    published    communities    dalton    ecce    biology    mtb    aring    unlike    eccb    13    extrapulmonary    multidrug    eagerly    recognition    attractive    holo    mycp    slow    pulmonary    ancestral    substrates    complementary    protein   

Project "ESX-4 T7SS" data sheet

The following table provides information about the project.

Coordinator		 EUROPEAN MOLECULAR BIOLOGY LABORATORY 

Organization address
address: Meyerhofstrasse 1
city: HEIDELBERG
postcode: 69117
website: http://www.embl.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.
 Coordinator Country Germany [DE]
 Total cost 162˙806 €
 EC max contribution 162˙806 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-04-01   to  2021-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EUROPEAN MOLECULAR BIOLOGY LABORATORY DE (HEIDELBERG) coordinator 162˙806.00

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 Project objective

Mycobacterium abscessus (Mab) is an opportunistic-multidrug-resistant non-tuberculous mycobacteria responsible for multiple clinically-acquired infections both pulmonary and extrapulmonary. Unlike many rapidly growing mycobacteria (RGM), Mab is able to survive and multiply within macrophages, similar to slow growing mycobacteria (SGM) such as M. tuberculosis (Mtb). In Mtb, five T7SS (ESX-1-5) have been identified and shown to be essential for intracellular survival (ESX-1), virulence (ESX-1 and ESX-5) or growth (ESX-3). T7SS are composed of five protein components essential for function: EccB, EccC, EccD, EccE and MycP. Except for a low-resolution structure of the holo ESX-5 complex from the host lab at 13 Å resolution, no structural data on any T7SS have been published to date, rendering structural work timely and eagerly awaited by relevant communities. Deemed inactive due to its lack of one of the established T7SS components EccE4, ESX-4 has been considered an ancestral T7SS form. However, Mab possess a fully intact and functional ESX-4, essential for its intracellular survival, rendering it a highly attractive target for an in-depth characterization. Here, I propose an interdisciplinary project that includes both functional and structural investigation. As the 2 M Dalton-holo-complex crosses the Mab inner membrane, experimental structural work will be challenging and require an integrative modeling approach to combine diverse experimental data sets. Complementary infection biology experiments including microbiology, genetics and cell biology will be carried out by collaborators. With this work, I aim to respond to central questions related to T7SS in general and Mab ESX-4 specifically, such as: what is the mechanism of T7SS-mediated secretion? What makes ESX-4 specific and different from other T7SS? What is the specific role of EccE4 to establish a functionally active ESX4? and What are the substrates and specific mechanism of ESX-4 substrate recognition?

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