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Deciphering the early events of the transcriptional dialogue between Aspergillus fumigatus and Pseudomonas aeruginosa in a dual-species biofilm

ABSTRACT: The polymicrobial biofilm formed by Aspergillus fumigatus and Pseudomonas aeruginosa is clinically significant, particularly in the airways of cystic fibrosis patients, yet the initial transcriptional reprogramming underlying this interaction remains poorly characterized. This study employs dual-species RNA sequencing to decipher the early (48-hour) transcriptional dialogue within a co-culture biofilm model. We reveal that P. aeruginosa adopts a profound state of metabolic arrest and nutrient scavenging when confronted with wild-type A. fumigatus, characterized by a paradoxical downregulation of iron acquisition machinery and a global shift towards transport activity and alternative nutrient catabolism. In response, A. fumigatus exhibits metabolic repression coupled with the induction of stress defense and alternative energy pathways. Disruption of the fungal histidine kinase SlnA, a key signaling component, dramatically alters this interkingdom crosstalk. In the presence of the ΔslnA mutant, P. aeruginosa reactivates canonical starvation responses, including siderophore production and chemotaxis, while the mutant fungus fails to mount an appropriate structural and chemical defense, displaying a transcriptional profile of dysregulated metabolism and vulnerability. Furthermore, the interaction bidirectionally modulates the expression of virulence determinants and secondary metabolite gene clusters in both species, a process significantly influenced by the slnA locus. Our findings define the early transcriptional landscape of this critical fungal-bacterial interaction and establish SlnA as a master regulator of fungal adaptation within a competitive polymicrobial niche.

ORGANISM(S): Aspergillus fumigatus Pseudomonas aeruginosa

PROVIDER: GSE335207 | GEO | 2026/06/19

REPOSITORIES: GEO

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			Action	DRS
		Other
	GSE335207_RNAseq_A_fumigatus.csv.gz	Csv
	GSE335207_RNAseq_P_aeruginosa.csv.gz	Csv

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Project description:The interaction of clinically relevant microorganisms is the focus of various studies, e.g. the interaction between the pathogenic yeast, Candida albicans, and the bacterium, Pseudomonas aeruginosa and these interactions can alter the outcome of infection, growth dynamics of each species and antimicrobial resistance of pathogens. During infection, both C. albicans and P. aeruginosa can elicit the release arachidonic acid (AA) from host cells membranes through the action of phospholipases. This polyunsaturated fatty acid can be transformed into immune-modulating compounds, termed eicosanoids, by both host-derived and microbial-derived enzymatic reactions. In its free form, AA can affect the growth of both C. albicans and P. aeruginosa, inhibiting the morphogenesis of C. albicans as well as reducing resistance towards antifungal agents. However, the mechanism of this is unknown. Previous studies on the effect of polyunsaturated fatty acids have indicated a possible alteration in plasma membrane organisation and permeability. Our group aimed to address how AA affects C. albicans in both single species biofilms, as well as in polymicrobial biofilms with P. aeruginosa. RNAseq was performed on single and polymicrobial biofilms in the presence and absence of a sub-inhibitory (100 µM) concentration of AA. Differential expression was determined between C. albicans single species biofilms in the presence and absence of AA. Secondly, the influence of co-incubation of C. albicans with P. aeruginosa in the absence of AA was evaluated to identify novel facets of interaction not previously identified, and to establish a baseline to determine the effect of AA on C. albicans in polymicrobial biofilms. Lastly, the effect of AA on C. albicans in polymicrobial biofilms was determined through comparison with polymicrobial biofilms in the absence of AA. This study provides a comprehensive analysis of the effect of AA and both co-incubation of C. albicans with P. aeruginosa focused on the transcriptome.

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Deciphering the early events of the transcriptional dialogue between Aspergillus fumigatus and Pseudomonas aeruginosa in a dual-species biofilm

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