H2020Индивидуална стипендия2018–2019

ACtIVAtE · The virulence potential of human pathogens: how Acinetobacter baumannii survives Acanthamoeba castellanii predation

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

Период: 2018-01-01 → 2019-12-31
Финансиране от ЕС: 172 800 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Бактерията Acinetobacter baumannii и нейните механизми за оцеляване се изучават чрез взаимодействието ѝ с амебата Acanthamoeba castellanii. Познаването на тези процеси помага за по-добрата борба с патогени, които са устойчиви на всички налични антибиотици.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

The virulence potential of human pathogens: how Acinetobacter baumannii survives Acanthamoeba castellanii predation

Antibiotics resistance is one of the most important modern health issue. With the apparition of pan-resistant bacteria (meaning resistant to all the commercially available antibiotics), it is urgent and crucial to find new antibiotics, but new fighting alternatives as well. In this context, the bacterial pathogen Acinetobacter baumannii was ranked as a top priority pathogen due to its worrying resistance arsenal (WHO 2017 and CDC 2019). Besides its antibiotic resistances, A. baumannii bacteria are highly resistant to environmental stresses and the human immune system. The study of this Gram-negative bacterium is rendered even more difficult by the fact that these bacteria are very heterogeneous, characterized by a dynamic genome due to horizontal gene transfer by natural competence. In other words, they can take up extracellular DNA fragments and integrate them in their genome to evolve and quickly acquire resistance genes. Seeing this whole diversity amongst A. baumannii isolates (both at the phenotypic and genotypic levels), it is not surprising that, nowadays, the virulence and the mechanisms of stress resistance still remain to be understood.A better understanding of the resistances mechanisms (not only for antibiotics) is crucial to better fight this multidrug resistant pathogen. In this context, we wanted to first determine if the few classical reference strains of A. baumannii available represent good bacterial models to study the current and modern multidrug clinical isolates. Then, based on our phenotypic observations, we generate an experimental strategy to work on the capsule production. We could also study this phenomenon using a new host-pathogen interaction based on the phagocytic pressure exerted by the amoeba called Acanthamoeba castellanii. The aim being to develop a new infection model to study common resistance mechanism, shared by the majority of the current and modern clinical isolates. A better understanding of the resistance mechanisms is important for the development of further antimicrobial strategies.Beside this fundamental part of the project, we wanted to follow a more applied strategy, and also screened a compounds library to find new antibiotics against multidrug-resistant A. baumannii bacteria.

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

Цел на проекта

The human pathogen Acinetobacter baumannii represents a deadly threat to human health. Despite its established clinical relevance, the pathogenicity of this nosocomial superbug is poorly understood. The biphasic amoeba Acanthamoeba castellanii is a cellular infection model broadly used to decipher the virulence mechanisms of human pathogens, as bacterial resistance upon amoebal predation (grazing) are often correlated with their pathogenicity potential in human. However, high-throughput screening approaches to investigate the virulence mechanisms of A. baumannii using this amoeba in an infection context are still lacking.This project aims at applying original large-scale screening approaches to identify A. baumannii virulence factors using the amoeba A. castellanii as host-pathogen system. The proposed experimental set up allows monitoring the outcome of the bacteria-amoebae interactions in qualitative and quantitative manners, at both population and single cell levels. Virulence induction of A. baumannii, as well as the use of successful clinical isolates will be tested using several complementary grazing assays. Precise localization of A. baumannii reporter strains will be done on both trophozoite and cyst stages of A. castellanii, complemented with (i) real-time and live-cell fluorescence imaging as well as (ii) electron microscopy techniques. Viability assays for both bacteria and amoebae will be done to understand the symbiotic outcome of this interaction. The global resistance potential of A. baumannii will be assessed by (i) Tn-seq analysis and (ii) high-throughput screen of individual mutant strains, followed by in depth mechanistic studies on validated attenuated strains.This project will shed light on the yet unknown global virulence mechanisms of A. baumannii by generating original screening methods using A. castellanii as an infection cellular model.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITE DE NAMUR · NamurКоординаторБелгия