The fungal transcription factor SmpR coordinates secondary metabolism and antibacterial defence in Aspergillus fumigatus during interspecies interaction

Le résumé fourni par la source

ABSTRACT Aspergillus fumigatus , an opportunistic human fungal pathogen, encodes numerous secondary metabolite biosynthetic gene clusters (BGCs) that are tightly regulated and often remain silent under standard conditions. Co-cultivation with Streptomyces rapamycinicus or treatment with the secondary metabolite from this species, the arginoketide azalomycin F, induce the otherwise silent fumicycline ( fcc ) BGC of A. fumigatus . To elucidate the underlying regulatory circuitry, we performed transcriptome analyses of A. fumigatus exposed to azalomycin F or co-cultured with S. rapamycinicus . Both conditions triggered a coordinated antibacterial response, characterized by induction of specific secondary metabolites and antibacterial effectors, alongside repression of other BGCs, including those for fusarinine C, pyripyropene A, and fumagillin. Among the most strongly induced genes was a zinc cluster transcription factor, designated SmpR for s econdary metabolite m ultiple p athway regulator, which is conserved within Ascomycota. SmpR expression was selectively induced by azalomycin F, specific Streptomyces species and other bacteria isolated from soil such as Kribbella spp. and Arthrobacter spp.. Functional analyses revealed that SmpR is required for activation of the fumicycline BGC: its deletion reduced, whereas its overexpression enhanced fumicycline production independently of external stimuli. We further demonstrate that SmpR acts upstream of the pathway-specific regulator FccR and additionally controls multiple antibacterial BGCs, including those for hexadehydroastechrome, helvolic acid and xanthocillin. Together, our data identify SmpR as a key regulator coordinating antibacterial secondary metabolism in response to bacterial signals in A. fumigatus .

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.