AUTHOR=Reece Emma , Doyle Sean , Greally Peter , Renwick Julie , McClean Siobhán 

TITLE=Aspergillus fumigatus Inhibits Pseudomonas aeruginosa in Co-culture: Implications of a Mutually Antagonistic Relationship on Virulence and Inflammation in the CF Airway

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01205

DOI=10.3389/fmicb.2018.01205

ISSN=1664-302X

ABSTRACT=<p>Many cystic fibrosis (CF) airway infections are considered to be polymicrobial and microbe–microbe interactions may play an important role in disease pathology. <italic>Pseudomonas aeruginosa</italic> and <italic>Aspergillus fumigatus</italic> 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 <italic>P. aeruginosa</italic>. Our objective was to examine the interactions between <italic>A. fumigatus</italic> and <italic>P. aeruginosa</italic>, specifically the effects of co-colonization on biofilm formation, virulence and host pro-inflammatory responses. Our findings suggest that co-infections of <italic>A. fumigatus</italic> and <italic>P. aeruginosa</italic> in the <italic>Galleria mellonella</italic> acute infection model showed that pre-exposure of larvae to sub-lethal inocula of <italic>A. fumigatus</italic> increased the mortality caused by subsequent <italic>P. aeruginosa</italic> infection. Co-infection of human bronchial epithelial cells (CFBE41o<sup>-</sup>) 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. <italic>A. fumigatus</italic> 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 <italic>A. fumigatus</italic> colonizing the CF airways may have a significant impact on the CF airway microbiome composition with potential clinical implications.</p>