Studies of Pseudomonas aeruginosa Mutants Indicate Pyoverdine as the Central Factor in Inhibition of Aspergillus fumigatus Biofilm.

Autor: Sass G; California Institute for Medical Research, San Jose, California, USA., Nazik H; California Institute for Medical Research, San Jose, California, USA.; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.; Department of Microbiology, Istanbul University, Istanbul, Turkey., Penner J; California Institute for Medical Research, San Jose, California, USA., Shah H; California Institute for Medical Research, San Jose, California, USA., Ansari SR; California Institute for Medical Research, San Jose, California, USA., Clemons KV; California Institute for Medical Research, San Jose, California, USA.; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA., Groleau MC; INRS-Institut Armand-Frappier, Laval, Quebec, Canada., Dietl AM; Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Visca P; Department of Sciences, Roma Tre University, Rome, Italy., Haas H; Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Déziel E; INRS-Institut Armand-Frappier, Laval, Quebec, Canada., Stevens DA; California Institute for Medical Research, San Jose, California, USA stevens@stanford.edu.; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Jazyk: angličtina
Zdroj: Journal of bacteriology [J Bacteriol] 2017 Dec 05; Vol. 200 (1). Date of Electronic Publication: 2017 Dec 05 (Print Publication: 2018).
DOI: 10.1128/JB.00345-17
Abstrakt: Pseudomonas aeruginosa and Aspergillus fumigatus are common opportunistic bacterial and fungal pathogens, respectively. They often coexist in airways of immunocompromised patients and individuals with cystic fibrosis, where they form biofilms and cause acute and chronic illnesses. Hence, the interactions between them have long been of interest and it is known that P. aeruginosa can inhibit A. fumigatus in vitro We have approached the definition of the inhibitory P. aeruginosa molecules by studying 24 P. aeruginosa mutants with various virulence genes deleted for the ability to inhibit A. fumigatus biofilms. The ability of P. aeruginosa cells or their extracellular products produced during planktonic or biofilm growth to affect A. fumigatus biofilm metabolism or planktonic A. fumigatus growth was studied in agar and liquid assays using conidia or hyphae. Four mutants, the pvdD pchE , pvdD , lasR rhlR , and lasR mutants, were shown to be defective in various assays. This suggested the P. aeruginosa siderophore pyoverdine as the key inhibitory molecule, although additional quorum sensing-regulated factors likely contribute to the deficiency of the latter two mutants. Studies of pure pyoverdine substantiated these conclusions and included the restoration of inhibition by the pyoverdine deletion mutants. A correlation between the concentration of pyoverdine produced and antifungal activity was also observed in clinical P. aeruginosa isolates derived from lungs of cystic fibrosis patients. The key inhibitory mechanism of pyoverdine was chelation of iron and denial of iron to A. fumigatus IMPORTANCE Interactions between human pathogens found in the same body locale are of vast interest. These interactions could result in exacerbation or amelioration of diseases. The bacterium Pseudomonas aeruginosa affects the growth of the fungus Aspergillus fumigatus Both pathogens form biofilms that are resistant to therapeutic drugs and host immunity. P. aeruginosa and A. fumigatus biofilms are found in vivo , e.g., in the lungs of cystic fibrosis patients. Studying 24 P. aeruginosa mutants, we identified pyoverdine as the major anti- A. fumigatus compound produced by P. aeruginosa Pyoverdine captures iron from the environment, thus depriving A. fumigatus of a nutrient essential for its growth and metabolism. We show how microbes of different kingdoms compete for essential resources. Iron deprivation could be a therapeutic approach to the control of pathogen growth.
(Copyright © 2017 American Society for Microbiology.)
Databáze: MEDLINE