Project description:Pseudomonas aeruginosa is a re-emerging opportunistic pathogen with broad antimicrobial resistance. We have previously reported that the major siderophore pyoverdine from this pathogen disrupts mitochondrial networks and induces a lethal hypoxic response in model host Caernorhabditis elegans. However, the mechanism of such cytotoxicity remained unclear. Here, we demonstrate that pyoverdine translocates into host cells, binding to host ferric iron sources. The reduction of host iron content disrupts mitochondrial function such as NADH oxidation and ATP production and activates mitophagy. This activates a specific immune response that is distinct from colonization-based pathogensis and exposure to downstream pyoverdine effector Exotoxin A. Host response to pyoverdine resembles that of a hypoxic crisis or iron chelator treatment. Furthermore, we demonstrate that pyoverdine is a crucial virulence factor in P. aerguinosa pathogenesis against cystic fibrosis patients; ΔF508 mutation in human CFTR increases susceptibility to pyoverdine-mediated damage.
Project description:A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence
Project description:Lactoferrin is a highly multifunctional protein. Indeed, it is involved in many physiological functions, including regulation of iron absorption and immune responses. We use microarrays to study the global genome expression of C. elegans fed with a nutraceutical product based on encapsulated lactoferrin.
Project description:ra13-03_pyo - effect of pseudomonas fluorescens pyoverdine on a.thaliana defence responses and iron homeostasis - Analyse de l’effet d’un traitement par la pyoverdine sur les gènes liés à l’homéostasie du fer et à l’induction des réactions de défense. - Arabidopsis thaliana plants cultivated in hydroponic conditions were treated for 3 days by pyoverdin, a bacteriosiderophore from Pseudomonas fluorescens C7R12 in a medium supplemented or deprived of iron.
Project description:ra13-03_pyo - effect of pseudomonas fluorescens pyoverdine on a.thaliana defence responses and iron homeostasis - Analyse de l’effet d’un traitement par la pyoverdine sur les gènes liés à l’homéostasie du fer et à l’induction des réactions de défense. - Arabidopsis thaliana plants cultivated in hydroponic conditions were treated for 3 days by pyoverdin, a bacteriosiderophore from Pseudomonas fluorescens C7R12 in a medium supplemented or deprived of iron. 12 dye-swap - organ comparison,treated vs untreated comparison
