H2020Индивидуална стипендия2016–2018

T6SS-PSEUDO-LIP · Type VI-dependent Pseudomonas aeruginosa phospholipases and host manipulation

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

Период: 2016-02-01 → 2018-01-31
Финансиране от ЕС: 195 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Бактерията Pseudomonas aeruginosa използва специални протеини (фосфолипази), за да прониква в човешките клетки и да променя процесите в тях. Разбирането на този механизъм помага да се разбере как бактерията предизвиква инфекции и се бори с имунната система.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Type VI-dependent Pseudomonas aeruginosa phospholipases and host manipulation

Pseudomonas aeruginosa is an extracellular Gram-negative bacterium able to cause healthcare associated infections, including pneumonia, urinary tract infections, wound infections, acute otitis and septicaemia. It is a major cause of chronic infection in patients with cystic fibrosis and on the World Health Organization list of antibiotic resistant priority pathogens. Like many other Gram-negative bacteria, P. aeruginosa manipulates eukaryotic host cells using secreted effectors and notably the type III secretion system (T3SS)-dependent exoenzymes ExoS, ExoT, ExoY and ExoU. More recently the type VI secretion system (T6SS) was shown to secrete anti-bacterial toxins and thus help outcompeting and manipulating the resident microbiota in the host. However, it has also been demonstrated that T6SS-effectors, such as PldA and PldB phospholipases, are injected into eukaryotic host cells and promote bacterial internalization or activation of several essential eukaryotic processes, such as triggering of the mitogen-activated protein kinase (MAPK) pathway or autophagy. P. aeruginosa T3SS and T6SS could thus be seen as effector-injecting nanomachines manipulating the host for bacterial benefit. The aims of this project were to study the expression of PldA and PldB in clinical isolates of P. aeruginosa (WP1), to decipher the role of PldA and PldB as virulence factor during in vivo infection using a murine model of respiratory tract infection (WP3), to analyze if PldA might play a major role in the H2-T6SS mediated entry of P. aeruginosa in non-phagocytic cells (WP4) and studied downstream signalling events that might occur upon Pld-dependent P. aeruginosa entry in non-phagocytic cells (WP5).

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

Цел на проекта

IntroductionPseudomonas aeruginosa (Pa), a nosocomial pathogen, secretes a wide range of virulence factors. A recently described secretion pathway is the type VI secretion system (T6SS). Pa encodes three T6SSs, H1-, H2- and H3-T6SS. The best-characterized H1-T6SS is involved in delivering toxins into bacterial competitors.State-of-the artTwo phospholipases (Pld), PldA and PldB secreted via H2- and H3-T6SS, respectively, were recently identified as trans-kingdom virulence effectors, triggering both killing of bacterial competitors and internalization into non-phagocytic cells. They are encoded within two distinct pld clusters that are not present in all Pa isolates.ObjectivesOur study should (i) decipher the prevalence of the two pld clusters among Pa isolates, (ii) elucidate the role of those Pld during in vivo infection, (iii) confirm the Pld contribution in the T6SS mediated entry, (iv) dissect the PI3K/Akt signalling pathway activation mediated by Pld during Pa entry.Overview of the actionThe aim is to link the fundamental study of new virulence factors with their relevance into clinical isolates.MethodsPa strains isolated from infection or environment will be screened for the expression of pld clusters. The role of PldA and PldB as virulence factor will be assessed using a murine model of respiratory tract infection. In vitro invasion assays will be performed to validate the role of PldA in the H2-T6SS-dependent entry in non-phagocytic cells. Upstream and downstream signalling events of Akt phosphorylation induced by PldA and PldB upon infection will be dissected by performing cell infections with mutants and specific inhibitors.Originality and innovative aspects of the projectBacteria-host interaction mechanisms are instrumental in the development of infectious diseases. Basic (host laboratory) and clinical (the applicant) research will join to characterize a newly discovered virulence strategy of Pa.

Оригинален текст от CORDIS (на английски).

Участници

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonКоординаторОбединеното кралство