Cystic Fibrosis isolates of Pseudomonas aeruginosa retain iron-regulated antimicrobial activity against Staphylococcus aureus through the action of multiple alkylquinolones

Nguyen, Angela T. and Jones, Jace W. and Cámara, Miguel and Williams, Paul and Kane, Maureen A. and Oglesby-Sherrouse, Amanda G. (2016) Cystic Fibrosis isolates of Pseudomonas aeruginosa retain iron-regulated antimicrobial activity against Staphylococcus aureus through the action of multiple alkylquinolones. Frontiers in Microbiology, 7 . ISSN 1664-302X

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Abstract

Cystic fibrosis (CF) is a hereditary disease that predisposes individuals to pulmonary dysfunction and chronic infections. Early infection of the CF lung with Staphylococcus aureus is common, while Pseudomonas aeruginosa becomes dominant as disease progresses. Emergence of P. aeruginosa likely depends on the action of multiple 2-alkyl-4-(1H)-quinolones (AQ) secreted by this organism. We recently showed that antimicrobial activity against S. aureus is enhanced by iron depletion and is dependent upon multiple AQ metabolites. Two of these AQs, the Pseudomonas quinolone signal [PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone] and 2-heptyl-4-hydroxyquinoline (HHQ), are quorum sensing molecules that activate the expression of multiple microbicidal factors. Here we show for the first time that HHQ also exhibits innate antimicrobial activity against S. aureus. We further show that iron depletion potentiates the antistaphylococcal activity of HHQ, as well as 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), another AQ that functions as a cytochrome B inhibitor. Notably, we found that deletion of the genes for the terminal biosynthetic steps for either PQS or HQNO results in overproduction of the HHQ intermediate, likely maintaining the ability of these mutants to mediate antimicrobial activity. Compensatory increases in HHQ were also observed in PQS-deficient CF isolates, which also retained the ability to mediate iron-regulated antimicrobial activity against S. aureus. These studies demonstrate that iron-regulated antimicrobial activity of P. aeruginosa against S. aureus is due to the cumulative effects of multiple AQ metabolites, both the production and activity of which are modulated by environmental iron levels.

Item Type: Article
Additional Information: This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission
Keywords: Pseudomonas aeruginosa, iron regulation, AQs, Staphylococcus aureus, quorum sensing
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Molecular Medical Sciences
Identification Number: https://doi.org/10.3389/fmicb.2016.01171
Depositing User: Eprints, Support
Date Deposited: 16 Aug 2016 07:34
Last Modified: 17 Sep 2016 19:52
URI: http://eprints.nottingham.ac.uk/id/eprint/35860

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