Molecular Modifications of the Pseudomonas Quinolone Signal in the Intermicrobial Competition with Aspergillus.

Hasan Nazik,Eric Déziel,Paul Williams,David A Stevens,Gabriele Sass

doi:10.3390/jof7050343

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.

Highlights

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) encounter each other in nature in soil and water, and are, in most studies, the most frequently found bacterium and fungus in the airways of immunocompromised hosts, including persons with cystic fibrosis (CF) [1,2]
Pseudomonas Quinolone Signal (PQS) is a quorumsensing molecule, coordinating many Pa functions [8,10]. It chelates iron (Fe) and delivers it to the bacterial cell membrane in conjunction with Pa siderophores [10,11,12,13]. It upregulates genes involved in Pa oxidative stress responses, but can be a pro-oxidant and induce oxidative stress; it regulates Pa virulence factors, and in intermicrobial interactions it can be used as a quorum sensing signal by other bacterial species, inhibit the respiratory chain, or induce membrane vesicle formation in other bacteria; and it can be inactivated by other bacteria [14,15,16]
In an overview of the present studies, every congener studied was inhibitory to Af biofilm, with exception of C1-PQS

Summary

Introduction

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) encounter each other in nature in soil and water, and are, in most studies, the most frequently found bacterium and fungus in the airways of immunocompromised hosts, including persons with cystic fibrosis (CF) [1,2]. PQS is a quorumsensing molecule, coordinating many Pa functions [8,10] It chelates iron (Fe) and delivers it to the bacterial cell membrane in conjunction with Pa siderophores [10,11,12,13]. It upregulates genes involved in Pa oxidative stress responses, but can be a pro-oxidant and induce oxidative stress; it regulates Pa virulence factors, and in intermicrobial interactions it can be used as a quorum sensing signal by other bacterial species, inhibit the respiratory chain, or induce membrane vesicle formation in other bacteria; and it can be inactivated by other bacteria [14,15,16].

Methods

Results

Conclusion