Reece, Emma and Doyle, Sean and Greally, Peter and Renwick, Julie and McClean, Siobhan (2018) Aspergillus fumigatus Inhibits Pseudomonas aeruginosa in Co-culture: Implications of a Mutually Antagonistic Relationship on Virulence and Inflammation in the CF Airway. Frontiers in Microbiology, 9 (1205). ISSN 1664-302X

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Abstract

Many cystic fibrosis (CF) airway infections are considered to be polymicrobial and microbe–microbe interactions may play an important role in disease pathology. Pseudomonas aeruginosa and Aspergillus fumigatus are the most prevalent bacterial and fungal pathogens isolated from the CF airway, respectively. We have previously shown that patients co-colonized with these pathogens had comparable outcomes to those chronically colonized with P. aeruginosa. Our objective was to examine the interactions between A. fumigatus and P. aeruginosa, specifically the effects of co-colonization on biofilm formation, virulence and host pro-inflammatory responses. Our findings suggest that co-infections of A. fumigatus and P. aeruginosa in the Galleria mellonella acute infection model showed that pre-exposure of larvae to sub-lethal inocula of A. fumigatus increased the mortality caused by subsequent P. aeruginosa infection. Co-infection of human bronchial epithelial cells (CFBE41o-) with both pathogens did not enhance IL-6 and IL-8 production beyond the levels observed following single infections. In addition, both pathogens stimulated cytokine secretion via the same two mitogen-activated protein kinases (MAPKs) signaling pathways, ERK and p38. Mixed species biofilms showed overall reduced biofilm development with crystal violet staining. Quantification by species-specific qPCR revealed that both pathogens had mutually antagonistic effects on each other. A. fumigatus supernatants showed strong anti-Pseudomonal activity and gliotoxin was the main active agent. Gliotoxin resulted in varying levels of anti-biofilm activity toward other bacteria commonly found in the CF airways. Gliotoxin produced by A. fumigatus colonizing the CF airways may have a significant impact on the CF airway microbiome composition with potential clinical implications.

Item Type:	Article
Additional Information:	Copyright © 2018 Reece, Doyle, Greally, Renwick and McClean. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Cite as: Reece E, Doyle S, Greally P, Renwick J and McClean S (2018) Aspergillus fumigatus Inhibits Pseudomonas aeruginosa in Co-culture: Implications of a Mutually Antagonistic Relationship on Virulence and Inflammation in the CF Airway. Front. Microbiol. 9:1205. doi: 10.3389/fmicb.2018.01205
Keywords:	co-colonization; cystic fibrosis; Aspergillus fumigatus; Pseudomonas aeruginosa; biofilm; inflammation; gliotoxin;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	11153
Identification Number:	https://doi.org/10.3389/fmicb.2018.01205
Depositing User:	Dr. Sean Doyle
Date Deposited:	08 Oct 2019 14:01
Journal or Publication Title:	Frontiers in Microbiology
Publisher:	Frontiers
Refereed:	Yes
URI:	https://www.frontiersin.org/
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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