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

Informations projet

ESX-4 T7SS

N° de convention de subvention: 846476

DOI

10.3030/846476

Projet clôturé

Date de signature de la CE 21 Mars 2019

Date de début 1 Avril 2019

Date de fin 31 Mars 2021

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 162 806,40

Contribution de l’UE

€ 162 806,40

Coordonné par

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany

Periodic Reporting for period 1 - ESX-4 T7SS (Structure/function of a prototypic type VII secretion system from a fast-growing pathogenic mycobacteria)

Période du rapport: 2019-04-01 au 2021-03-31

Résumé du contexte et des objectifs généraux du projet

Mycobacteria are pathogens responsible for many infamous and widely spread diseases, like tuberculosis or leprosis. At the start of this project, no potent vaccines were available against mycobacteria and with the rise of multiple multi-drug resistant strains of mycobacteria, new drugs were needed. Though concerning, the World Health Organization (WHO) was still, with extensive efforts, optimistically hoping to eradicate TB by 2035. At the end of this study, however, the WHO stated that due to the COVID pandemic, their efforts in eradicating the century old disease were predicted to experience at least a 7-year set-back.
This project aimed at studying a secretion system, specific to mycobacteria, called the Type VII Secretion system (T7SS). T7SS allows the bacteria to import important nutrients, while exporting virulent factors that lets the bacteria evade the human immune system. Therefore, this makes this study of T7SS so attractive: if we could design a drug that would block the import of essential nutrient for the bacteria, we could starve it to death; or we could attempt to block the secretion of the virulent factors and let our immune system take care of the bacteria. During this project, information was gathered on the 3D structure of the T7SS complex machinery and, in collaboration with laboratories from Germany and France, more information was gathered on the factors secreted by T7SS and their impact on our immune system.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Since the beginning of this project, substantial efforts were made toward the 3D resolution of the Mycobacterium abscessus ESX-4 type VII secretion system. Therefore, the complex, and its multiple copies of the five different proteins that composes it, was successfully purified and promising results toward its structure resolution were obtained. Invaluable information was also gathered on two of the five proteins composing the secretion system. Finally, extensive information, in collaboration with the research center of Borstel (Germany), and the University of Versailles and the IRIM institute of Montpellier (France), were obtained on the virulent factors secreted by Mycobacterium abscessus ESX-4. A literature review of the progress made in the field was also recently accepted by Microbiology, a Microbiology Society journal. This review was written in collaboration with members of all four laboratories.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Beyond the state-of-the-art and the release of the literature review, we are expecting to release another paper within the year on the secreted factors. It will provide additional information on the behavior of Mycobacteria abscessus and its interaction with the human immune system, helping clinician better understand the bacteria and better care for their patient.

Model of ESX-4 imbedded within the complex membrane of Mycobacterium abscessus.