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

Información del proyecto

ESX-4 T7SS

Identificador del acuerdo de subvención: 846476

DOI

10.3030/846476

Proyecto cerrado

Fecha de la firma de la CE 21 Marzo 2019

Fecha de inicio 1 Abril 2019

Fecha de finalización 31 Marzo 2021

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 162 806,40

Aportación de la UE

€ 162 806,40

Coordinado por

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)

Período documentado: 2019-04-01 hasta 2021-03-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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.