H2020Индивидуална стипендия2021–2023

HADES · Functional mechanism of heparin-binding hemagglutinin adhesin from Mycobacterium tuberculosis

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-02-01 → 2023-07-02
Финансиране от ЕС: 171 473 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Протеинът HBHA помага на бактериите, причиняващи туберкулоза, да се закрепят за епителните клетки и да се разпространяват извън белите дробове. Разбирането на този механизъм помага при разработването на по-добри методи за диагностика и нови терапевтични цели.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Functional mechanism of heparin-binding hemagglutinin adhesin from Mycobacterium tuberculosis

The HADES project tackles a crucial issue related to the pathogenesis of Tuberculosis (TB), the leading global cause of death from an infectious bacterial agent. Specifically, the project aims to shed light on the poorly understood process of TB extrapulmonary dissemination, which relies on a virulence factor called heparin-binding haemagglutinin adhesin (HBHA). HBHA is a mycobacterial cell surface protein, and it plays pivotal role in MTB pathogenesis, promoting its adhesion to epithelial cells. Despite its relevance in the dissemination of TB, and as powerful diagnostic antigen or potential therapeutic target, there is only a limited understanding of the biological properties of HBHA. The project integrates complementary research programmes in structural biology and MTB microbiology, to characterize at high resolution the structural basis of the function of HBHA in different phases of the MTB life cycle and to provide the details of the underlying mechanism by which the extrapulmonary dissemination of TB is originated.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Tuberculosis (TB) is one of the most aberrant causes of global mortality and the molecular mechanisms of its pathogenesis are not well understood. The extrapulmonary dissemination of TB involves requires a crucial virulence factor designated as heparin-binding haemaglutinin adhesin (HBHA). HBHA is a 28 kDa dimeric protein localised at the surface of the Mycobacterium tuberculosis (MTB) that binds dextran sulphate, dermatan sulphate, glycosaminoglycans and heparan-sulphate proteoglycans thus mediating the adhesion with epithelial cells and to extracellular matrix components. Despite a crucial role in the dissemination of TB, a key relevance as strong diagnostic antigen and as therapeutic target, there is currently limited understanding of the structure and mechanism of action of HBHA.The ambitious aim of this proposal is to characterise at high-resolution the mechanisms of function of HBHA in different phases of the life cycle of MTB. To achieve this ambitious target, we will carry out an integrated investigation of solution-state and solid-state NMR nuclear magnetic resonance (NMR) to acquire high-resolution data on the interaction of HBHA with membranes of MTB. The NMR experiments will be complemented with biophysical studies and mutagenesis to accurately define the relationship between structure, dynamics and function of HBHA.Our preliminary data suggest that this ambitious project comes at the most opportune time as we now have tools, materials and knowledge to resolve this important goal for biochemistry and reveal the propeties of a crucial molecule for the mechanism of extrapulmonary dissemination of TB.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II · NapoliКоординаторИталия