Abstract
Different bacteria and fungi live as commensal organisms as part of the human microbiota, but shifts to a pathogenic state potentially leading to septic infections commonly occur in immunocompromised individuals. Several studies have reported synergistic or antagonistic interactions between individual bacteria and fungi which might be of clinical relevance. Here, we present first evidence for the interaction between Klebsiella pneumoniae and several Aspergillus species including A. fumigatus, A. terreus, A. niger and A. flavus which cohabit in the lungs and the intestines. Microbiological and molecular methods were employed to investigate the interaction in vitro, and the results indicate that Klebsiella pneumoniae is able to prevent Aspergillus spp. spore germination and hyphal development. The inhibitory effect is reversible, as demonstrated by growth recovery of Aspergillus spp. upon inhibition or elimination of the bacteria, and is apparently dependent on the physical interaction with metabolically active bacteria. Molecular analysis of Klebsiella-Aspergillus interaction has shown upregulation of Aspergillus cell wall-related genes and downregulation of hyphae-related genes, suggesting that Klebsiella induces cell wall stress response mechanisms and suppresses filamentous growth. Characterization of polymicrobial interactions may provide the basis for improved clinical management of mixed infections by setting the stage for appropriate diagnostics and ultimately for optimized treatment strategies.
Highlights
Microbial interactions are part of the highly complex human microbiome
The results have shown that, in the presence of K. pneumoniae, Aspergillus species were not able to progress with hyphal development by demonstrating significantly decreased DNA contents compared to Aspergillus in single cultures (Fig. 1B), revealing that the inhibitory effect of K. pneumoniae on Aspergillus species is independent of the fungal growth stage
The results have shown that, upon contact with K. pneumoniae strains, the biofilm thickness of A. fumigatus was significantly decreased compared to A. fumigatus growing alone
Summary
Microbial interactions are part of the highly complex human microbiome. Mapping of the human microbiome has shown a wide diversity of bacteria and fungi occupying specific niches[1,2,3,4]. We aimed to investigate the interactions between select opportunistic fungal pathogens including different Aspergillus species and the clinically important bacterium Klebsiella pneumoniae. The cell wall plays an important role in mediating interactions with the external environment relevant for nutrient diffusion and molecule-based signalling It protects the cells from oxidative or osmotic stresses, and modulates the response to antimicrobial drugs[91,92,93,94,95]. It is important to point out that fungal spores and hyphae display different structures and compositions of the cell wall which can induce differential immune responses by the host[105,106]. We sought to investigate the interactions between four Aspergillus species including A. fumigatus, A. terreus, A. niger and A. flavus, and different strains of K. pneumoniae with low or high capacity of biofilm formation. Our observations highlight the importance of identifying the presence of polymicrobial infections and potential interactions between the pathogens with regard to optimized diagnostic approaches and appropriate antimicrobial treatment
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