H2020Индивидуална стипендия2021–2023

BranchOut · Filament branching during infection by a human opportunistic fungal pathogen

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

Период: 2021-09-01 → 2023-08-31
Финансиране от ЕС: 196 708 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Разклоняването на нишките при гъбичката Candida albicans помага за проникването ѝ в тъканите на човешкото тяло. Разбирането на този процес е важно, тъй като тези инфекции могат да доведат до тежки заболявания и смърт, особено при хора с отслабен имунитет.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Filament branching during infection by a human opportunistic fungal pathogen

Human fungal pathogens are responsible for over 1.6 million deaths and approximately billion of superficial mucosal infections worldwide each year. Aging and respiratory diseases increase the risk of invasive fungal disease that can also lead to severe illness and death. Last year, the World Health Organization (WHO) released a report recommending to ”focus and drive further research and policy interventions to strengthen the global response to fungal infections and antifungal resistance”. Four Candida spp. are highlighted on the released fungal priority list with C. albicans in the most critical group. C. albicans is an opportunistic fungal pathogen. It is found as a commensal in the mouth and gastrointestinal tract in ~ 50% of healthy adults. In specific conditions, the fungus becomes pathogenic, and causes an infection, candidiasis, which results from fungal proliferation. C. albicans, a dimorphic fungus, thrives in either budding or filamentous forms due to a complex interplay of signals and polarity-regulating proteins conserved among eukaryotic cells. Both morphologies coexist in tissues during systemic infection, with filaments promoting tissue invasion and damage, and budding cells facilitating mucosal colonization, dissemination, and biofilm formation. Filamentous growth, conserved in most fungi, comprises tubular filaments that extend and explore surroundings, enabling tissue invasion. The leading filament grows apically, often accompanied by branching to maximize the number of growing filament tips. Branching may occur at cell tips or within subapical compartments, with the latter, called lateral branching, being predominantly observed in C. albicans. Although branching is implicated in fungal virulence, its exact function remains enigmatic. In this project we aimed to understand filament branching addressing three questions: 1) Is branching distinct from the main filament? 2) Are branches responding differently to antifungal drugs? 3) Is branching important for fungal virulence? Our results so far show that branching is a distinct developmental state that contributes to the antifungal response and plays a potential role in pathogenicity. Branching is virtually present in all filamentous fungi, including those that has a major impact on our economy. Globally, fungal pathogens cause crop losses of 10-30% (0.1-0.2 trillion €) each year and $7.5 billion of direct medical costs in the U.S.A. alone. Research conducted in BranchOut has provided a major understanding of the so far unknown functions and regulation of branching, and its implication in virulence.

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

Цел на проекта

Fungal infections result in millions of deaths and billions of superficial infections each year. Morphological transitions are critical for fungal virulence. Filamentous hyphal branching is affected by nutrients and suggested to be altered during infection. The aim of this interdisciplinary project is to determine the importance of branching in the human opportunistic fungal pathogen Candida albicans. Specifically, how is branching controlled and regulated in time/space during infection? Towards this goal, I will investigate branching at the molecular/cellular levels, and use genetic/molecular perturbation to delineate functions and requirements of branching. Live-cell imaging will be used to determine the frequency and position of hyphal branching, as a function of infection-relevant conditions, including growth on/in different stiffness substrates, physical confinement, nutrients and gaseous environment. This will help us to characterize the biophysics of branching and to understand the spatial regulation of the process. To address how branching isaffected by host cells, this process will be followed in co-culture with reconstituted human epithelia To determine at molecular/cellular levels the critical processes and components that localize to incipient branch sites, I will use different fluorescent reporters. Targeted and unbiased, genetic/molecular approaches will be used to probe the functions and requirements of branching and selected mutants will be examined in mice. Using optogenetics, I will investigate perturbation of branching by induction of de novo branching. In summary, this interdisciplinary project, that takes advantage of cutting-edge imaging, molecular approaches and biophysics tools, will shed light on the importance and regulation of branching during fungal infections.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция