Novel intermicrobial molecular interaction: Pseudomonas aeruginosa Quinolone Signal (PQS) modulates Aspergillus fumigatus respon

Novel intermicrobial molecular interaction: Pseudomonas aeruginosa Quinolone Signal (PQS) modulates Aspergillus fumigatus response to iron | Microbiology Society
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1887
Microbiology
Volume 166, Issue 1
Research Article
Free
Novel intermicrobial molecular interaction:
Pseudomonas aeruginosa
Quinolone Signal (PQS) modulates
Aspergillus fumigatus
response to iron
Hasan Nazik
1​,2​
Gabriele Sass
1​,2​
Shajia R. Ansari
1​
Reyhan Ertekin
1​
Hubertus Haas
3​
Eric Déziel
4​
and
David A. Stevens
1​,2​
View Affiliations
Hide Affiliations
1​
California Institute for Medical Research, San Jose, CA, USA
2​
Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, USA
3​
Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
4​
INRS-Institut Armand-Frappier, Laval, Quebec, Canada
*Correspondence:
David A. Stevens,
[email protected]
Published:
22 November 2019
Abstract
Pseudomonas aeruginosa
(Pa) and
Aspergillus fumigatus
(Af), the commonest bacterium and fungus in compromised host airways, compete for iron (Fe). The Pseudomonas quinolone signal (PQS), a Pa quorum sensing molecule, also chelates Fe, and delivers Fe to the Pa cell membrane using Pa siderophores. In models of Af biofilm formation or preformed biofilms, PQS inhibited Af in a low Fe environment. AfΔ
sidA
(mutant unable to produce siderophores) biofilm was more sensitive to PQS inhibition than wild-type (WT), as was planktonic AfΔ
sidA
growth. PQS decreased WT Af growth on agar. All these inhibitory actions were reversed by Fe. The Pa siderophore pyoverdin, or Af siderophore inhibitor celastrol, act cooperatively with PQS in Af inhibition. These findings all indicate PQS inhibition is owing to Fe chelation.
Remarkably
, in high Fe environments
PQS
enhanced
Af biofilm at 1/100 to 1/2000 Fe concentration required for Fe alone to enhance. Planktonic Af growth, and on agar, Af conidiation, were also enhanced by PQS+Fe compared to Fe alone. In contrast, neither AfΔ
sidA
biofilm, nor planktonic AfΔ
sidA
, were enhanced by PQS-Fe compared to Fe. When Af siderophore ferricrocin (FC),+PQS, were added to AfΔ
sidA,
Af was then boosted more than by FC alone. Moreover, FC+PQS+Fe boosted AfΔ
sidA
more than Fe, FC, FC+Fe, PQS+FC or PQS+Fe. Thus PQS-Fe maximal stimulation requires Af siderophores. PQS inhibits Af via chelation under low Fe conditions. In a high Fe environment, PQS paradoxically stimulates Af efficiently, and this involves Af siderophores. PQS production by Pa could stimulate Af in cystic fibrosis airways, where Fe homeostasis is altered and Fe levels increase, supporting fungal growth.
Received:
07/06/2019
Accepted:
06/09/2019
Published Online:
22/11/2019
Keyword(s):
Aspergillus
Iron
PQS
and
Pseudomonas
Funding
This study was supported by the:
Child Health Research Institute, Stanford Transdisciplinary Initiatives Program
(Award CIMR no. 3777)
Principal Award Recipient:
Not Applicable
John Flatley
(Award CIMR no. 3770)
Principal Award Recipient:
Not Applicable
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Novel intermicrobial molecular interaction: Pseudomonas aeruginosa Quinolone Signal (PQS) modulates Aspergillus fumigatus response to iron
Microbiology
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