<i>Pseudomonas aeruginosa</i> Virulence Factors Support Voriconazole Effects on <i>Aspergillus fumigatus</i>

<i>Pseudomonas aeruginosa</i> and <i>Aspergillus fumigatus</i> are pathogens that are associated with deterioration of lung function, e.g., in persons with cystic fibrosis (CF). There is evidence that co-infections with these pathogens cause airway inflammation and aggravate...

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Main Authors: Gabriele Sass, Pallabi Shrestha, David A. Stevens
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/10/5/519
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author Gabriele Sass
Pallabi Shrestha
David A. Stevens
author_facet Gabriele Sass
Pallabi Shrestha
David A. Stevens
author_sort Gabriele Sass
collection DOAJ
description <i>Pseudomonas aeruginosa</i> and <i>Aspergillus fumigatus</i> are pathogens that are associated with deterioration of lung function, e.g., in persons with cystic fibrosis (CF). There is evidence that co-infections with these pathogens cause airway inflammation and aggravate pathology in CF lungs. Intermicrobial competition of <i>P. aeruginosa</i> and <i>A. fumigatus</i> has been described, but it is unknown how anti-fungal therapy is affected. The anti-fungal azole voriconazole (VCZ), supernatants of <i>P. aeruginosa</i> laboratory isolates PA14 or PAO1, or clinical isolate Pa10 independently inhibited biofilm metabolism of <i>A. fumigatus</i> isolates 10AF and AF13073. When VCZ and supernatants were combined at their IC<sub>50</sub>s, synergistic effects on <i>A. fumigatus</i> were found. Synergistic effects were no longer observed when <i>P. aeruginosa</i> supernatants were prepared in the presence of iron, or when <i>P. aeruginosa</i> mutants were lacking the ability to produce pyoverdine and pyochelin. Combination of pure <i>P. aeruginosa</i> products pyoverdine, pyochelin, and pyocyanin with VCZ showed synergistic anti-fungal effects. Combining VCZ with <i>P. aeruginosa</i> supernatants also improved its MIC and MFC against planktonic <i>A. fumigatus</i>. In summary, in the case of <i>P. aeruginosa</i>–<i>A. fumigatus</i> co-infections, it appeared that the <i>P. aeruginosa</i> co-infection facilitated therapy of the <i>Aspergillus</i>; lower concentrations of VCZ might be sufficient to control fungal growth.
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spelling doaj.art-9fbde9fc5c4141429e60980b57e4e3d72023-11-21T17:09:45ZengMDPI AGPathogens2076-08172021-04-0110551910.3390/pathogens10050519<i>Pseudomonas aeruginosa</i> Virulence Factors Support Voriconazole Effects on <i>Aspergillus fumigatus</i>Gabriele Sass0Pallabi Shrestha1David A. Stevens2California Institute for Medical Research, San Jose, CA 95128, USACalifornia Institute for Medical Research, San Jose, CA 95128, USACalifornia Institute for Medical Research, San Jose, CA 95128, USA<i>Pseudomonas aeruginosa</i> and <i>Aspergillus fumigatus</i> are pathogens that are associated with deterioration of lung function, e.g., in persons with cystic fibrosis (CF). There is evidence that co-infections with these pathogens cause airway inflammation and aggravate pathology in CF lungs. Intermicrobial competition of <i>P. aeruginosa</i> and <i>A. fumigatus</i> has been described, but it is unknown how anti-fungal therapy is affected. The anti-fungal azole voriconazole (VCZ), supernatants of <i>P. aeruginosa</i> laboratory isolates PA14 or PAO1, or clinical isolate Pa10 independently inhibited biofilm metabolism of <i>A. fumigatus</i> isolates 10AF and AF13073. When VCZ and supernatants were combined at their IC<sub>50</sub>s, synergistic effects on <i>A. fumigatus</i> were found. Synergistic effects were no longer observed when <i>P. aeruginosa</i> supernatants were prepared in the presence of iron, or when <i>P. aeruginosa</i> mutants were lacking the ability to produce pyoverdine and pyochelin. Combination of pure <i>P. aeruginosa</i> products pyoverdine, pyochelin, and pyocyanin with VCZ showed synergistic anti-fungal effects. Combining VCZ with <i>P. aeruginosa</i> supernatants also improved its MIC and MFC against planktonic <i>A. fumigatus</i>. In summary, in the case of <i>P. aeruginosa</i>–<i>A. fumigatus</i> co-infections, it appeared that the <i>P. aeruginosa</i> co-infection facilitated therapy of the <i>Aspergillus</i>; lower concentrations of VCZ might be sufficient to control fungal growth.https://www.mdpi.com/2076-0817/10/5/519<i>Pseudomonas aeruginosa</i><i>Aspergillus fumigatus</i>voriconazolemicrobial interactioncystic fibrosisdrug interaction
spellingShingle Gabriele Sass
Pallabi Shrestha
David A. Stevens
<i>Pseudomonas aeruginosa</i> Virulence Factors Support Voriconazole Effects on <i>Aspergillus fumigatus</i>
Pathogens
<i>Pseudomonas aeruginosa</i>
<i>Aspergillus fumigatus</i>
voriconazole
microbial interaction
cystic fibrosis
drug interaction
title <i>Pseudomonas aeruginosa</i> Virulence Factors Support Voriconazole Effects on <i>Aspergillus fumigatus</i>
title_full <i>Pseudomonas aeruginosa</i> Virulence Factors Support Voriconazole Effects on <i>Aspergillus fumigatus</i>
title_fullStr <i>Pseudomonas aeruginosa</i> Virulence Factors Support Voriconazole Effects on <i>Aspergillus fumigatus</i>
title_full_unstemmed <i>Pseudomonas aeruginosa</i> Virulence Factors Support Voriconazole Effects on <i>Aspergillus fumigatus</i>
title_short <i>Pseudomonas aeruginosa</i> Virulence Factors Support Voriconazole Effects on <i>Aspergillus fumigatus</i>
title_sort i pseudomonas aeruginosa i virulence factors support voriconazole effects on i aspergillus fumigatus i
topic <i>Pseudomonas aeruginosa</i>
<i>Aspergillus fumigatus</i>
voriconazole
microbial interaction
cystic fibrosis
drug interaction
url https://www.mdpi.com/2076-0817/10/5/519
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