H2020Индивидуална стипендия2019–2021

HGB-StIC · Human Genetic Basis of Severe Staphylococcal Infections in Childhood

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

Период: 2019-01-01 → 2021-12-31
Финансиране от ЕС: 260 930 €
Участници: 2
Схема: MSCA-IF-GF

Линиите свързват координатора с партньорите.

Накратко на български

Генетичните причини за тежки стафилококови инфекции при деца, като например вродени дефекти в имунната система, са в центъра на анализа. Разбирането на тези механизми помага да се обясни защо дори здрави деца развиват опасни за живота бактериални заболявания.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Human Genetic Basis of Severe Staphylococcal Infections in Childhood

Staphylococcus aureus is a prominent cause of bacterial infections in humans worldwide, especially in children. Invasive infections have a poor prognosis. Acquired risk factors for infections with S. aureus only account for a small proportion of severe infections, especially in the case of community-acquired infections. In fact, most cases of invasive staphylococcal diseases are unexplained as they strike otherwise healthy children. Known primary immune deficiencies collectively explain only a small minority of cases. Other inborn errors of immunity may account for a sizeable proportion of cases. The Researcher aims to identify and functionally characterize human gene(s) involved in susceptibility to S. aureus infections. State-of-the-art genetic approaches and cutting-edge immunological and microbiological methods are applied. By investigating human host counterparts in a genome-wide setting, this study is the first unbiased and systematic assessment linking S. aureus virulence factors with host genetic predisposition. During the Project, the Researcher has discovered an inborn error of immunity that, by disrupting cell-intrinsic immunity to a staphylococcal pore-forming toxin in non-hematopoietic cells, underlies life-threatening staphylococcal infections. This report spans the complete project, during which work was performed at The Rockefeller University (New York, U.S.A.) and the University Medical Center Utrecht (Utrecht, The Netherlands). At the time of reporting, the project has achieved most of its objectives and milestones and full achievement is expected on short term.

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

Цел на проекта

Staphylococcus aureus is one of the most important bacterial pathogens impacting human health. Beta-barrel pore-forming toxins (BB-PFTs) are major virulence factors of S. aureus that destroy phagocytes, key effectors of immunity during staphylococcal infection, in a receptor-specific manner. Acquired immunity to a specific compound of S. aureus, LTA, can rescue an inborn error of the TLR2 pathway (TIRAP deficiency). I hypothesize that severe staphylococcal infections during childhood, at least in some patients, can result from single gene inborn errors of immunity. Some of these disorders may affect immunity to BB-PFTs and the TLR2 pathway. In this project, a cohort of ±70 patients with severe S. aureus infections during childhood will be investigated for mutations responsible for a poor outcome of infection. I will perform whole exome sequencing in these patients and their parents. I will search for mutations in genes encoding BB-PFT-receptors and the TLR2 pathway. I will also search for mutations in a genome-wide approach, testing various genetic models and taking advantage, when appropriate, of genome-wide linkage. I will then functionally characterize the candidate mutations. Depending on the gene identified, a set of experiments will be performed to investigate the functional consequences of the morbid gene on immunity against S. aureus, and I will further characterize the specific host-pathogen interaction. This project will not only shed light on the pathogenesis of S. aureus, but will also provide the basis for new avenues of vaccine and treatment strategies. By investigating human host counterparts in a genome-wide setting, this study is the first unbiased and systematic assessment linking S. aureus virulence factors with host genetic predisposition.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAIR MEDISCH CENTRUM UTRECHT · UtrechtКоординаторНидерландия
THE ROCKEFELLER UNIVERSITY NOT FOR PROFIT CORPORATION · New YorkСъединени щати