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Molecular Modifications of the Pseudomonas Quinolone Signal in the Intermicrobial Competition with Aspergillus
Hasan Nazik1, Gabriele Sass1, Paul Williams2
1Infectious Diseases Research Laboratory, California Institute for Medical Research, San Jose, CA 95128, USA.
Abstract:
The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule for Pseudomonas aeruginosa that regulates virulence factors, chelates iron, and is an important factor in interactions with eukaryotes, including fungi and mammalian hosts. It was previously shown to inhibit or boost Aspergillus, depending on the milieu iron concentration. We studied several molecular modifications of the PQS molecule, and their effects on Aspergillus biofilm metabolism and growth in vitro, and the effects of iron supplementation. We found that most molecules inhibited Aspergillus at concentrations similar to that of PQS, but with relatively flat dose-responses, and all were less potent than PQS. The inhibition was reversible by iron, suggesting interference with fungal iron metabolism. Stimulation of Aspergillus was not noted. We conclude that the critical Aspergillus-inhibiting moeities of the PQS molecule were partially, but not completely, interfered with by molecular modifications at several sites on the PQS molecule. The mechanism, as with PQS, appears to relate to fungal iron metabolism.
Insights
Modified Pseudomonas quinolone signal (PQS) molecules inhibit Aspergillus growth by interfering with iron metabolism. This inhibition is reversible by iron, indicating a key role for iron in the interaction between PQS and Aspergillus.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Pseudomonas quinolone signal (PQS) is a quorum-sensing molecule from Pseudomonas aeruginosa.
- PQS influences virulence factors, iron chelation, and interactions with eukaryotes like fungi.
- PQS exhibits concentration-dependent effects on Aspergillus growth, modulated by iron availability.
Purpose of the Study:
- To investigate the effects of molecular modifications of PQS on Aspergillus biofilm metabolism and growth.
- To assess the impact of iron supplementation on these interactions.
- To understand the mechanism underlying PQS-mediated effects on Aspergillus.
Main Methods:
- Synthesis and testing of several PQS molecular modifications.
- In vitro assessment of Aspergillus biofilm metabolism and growth.
- Evaluation of iron supplementation effects on PQS-modified molecule activity.
Main Results:
- Most PQS modifications inhibited Aspergillus growth at concentrations similar to native PQS.
- Inhibitory effects showed relatively flat dose-responses and were less potent than PQS.
- Iron supplementation reversed the observed inhibition, suggesting interference with fungal iron metabolism.
- No stimulatory effects of PQS modifications on Aspergillus were observed.
Conclusions:
- Key Aspergillus-inhibiting components of PQS were partially affected by molecular modifications.
- The mechanism of inhibition, similar to native PQS, involves interference with fungal iron metabolism.
- Further research into PQS structure-activity relationships could yield novel antifungal strategies.
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