Inhibition of Aspergillus fumigatus and Its Biofilm by Pseudomonas aeruginosa Is Dependent on the Source, Phenotype and Growth Conditions of the Bacterium.

Jose A G Ferreira,Alfred M Spormann,Janus A J Haagensen,Elisabete Carolino,David A Stevens,Richard B Moss,Kevin Cohen,John C Penner,Karl V Clemons,Niaz Banaei,Hasan Nazik

doi:10.1371/journal.pone.0134692

Abstract

Aspergillus fumigatus (Af) and Pseudomonas aeruginosa (Pa) are leading fungal and bacterial pathogens, respectively, in many clinical situations. Relevant to this, their interface and co-existence has been studied. In some experiments in vitro, Pa products have been defined that are inhibitory to Af. In some clinical situations, both can be biofilm producers, and biofilm could alter their physiology and affect their interaction. That may be most relevant to airways in cystic fibrosis (CF), where both are often prominent residents.We have studied clinical Pa isolates from several sources for their effects on Af, including testing involving their biofilms. We show that the described inhibition of Af is related to the source and phenotype of the Pa isolate. Pa cells inhibited the growth and formation of Af biofilm from conidia, with CF isolates more inhibitory than non-CF isolates, and non-mucoid CF isolates most inhibitory. Inhibition did not require live Pa contact, as culture filtrates were also inhibitory, and again non-mucoid>mucoid CF>non-CF. Preformed Af biofilm was more resistant to Pa, and inhibition that occurred could be reproduced with filtrates. Inhibition of Af biofilm appears also dependent on bacterial growth conditions; filtrates from Pa grown as biofilm were more inhibitory than from Pa grown planktonically. The differences in Pa shown from these different sources are consistent with the extensive evolutionary Pa changes that have been described in association with chronic residence in CF airways, and may reflect adaptive changes to life in a polymicrobial environment.

Highlights

Cystic fibrosis (CF) is the result of mutations in the CF transmembrane conductance regulator affecting epithelial chloride and bicarbonate transport
Preformed Aspergillus fumigatus (Af) biofilm was more resistant to Pseudomonas aeruginosa (Pa), and inhibition that occurred could be reproduced with filtrates
The first was that of the effects of Pa on the development of biofilm by Af conidia and the second was that of the effects of Pa on preformed Af biofilm

Summary

Introduction

Cystic fibrosis (CF) is the result of mutations in the CF transmembrane conductance regulator affecting epithelial chloride and bicarbonate transport. The affected persons have defective mucociliary clearance and production of thick sticky mucus in which various pathogens can become entrapped This is a suitable environment for microbial growth and colonization, and these organisms or their soluble metabolites contribute to airway inflammation and subsequent damage. Af is ubiquitous in ambient air and the environment, and can be inhaled and subsequently establish residency Both organisms are proficient adapters to environmental stress and relatively resistant to current antimicrobials. They are suspected as important agents in promoting mucus plug formation in the airways, and both are known to form biofilms in vitro and in vivo [2,9,10,11,12,13,14,15,16,17,18,19,20]. Both pathogens are important because either can be an opportunist, causing invasive disease [35,36,37,38,39] or other complications [40,41], in lung transplantation, a therapeutic modality offered in debilitating CF

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