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Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates

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Autor(es):
Drott, M. T. [1, 2] ; Bastos, R. W. [3] ; Rokas, A. [4] ; Ries, L. N. A. [5] ; Gabaldon, T. [6, 7, 8] ; Goldman, G. H. [3] ; Keller, N. P. [1, 2] ; Greco, C. [1, 9]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 - USA
[2] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 - USA
[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo - Brazil
[4] Vanderbilt Univ, Dept Biol Sci, 221 Kirkland Hall, Nashville, TN 37235 - USA
[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto - Brazil
[6] ICREA, Barcelona - Spain
[7] Barcelona Supercomp Ctr, Life Sci Program, Barcelona - Spain
[8] Inst Res Biomed, Mech Dis Program, Barcelona - Spain
[9] John Innes Ctr, Dept Mol Microbiol, Norwich, Norfolk - England
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: MSPHERE; v. 5, n. 2 MAR-APR 2020.
Citações Web of Science: 0
Resumo

The filamentous fungus Aspergillus nidulans has been a primary workhorse used to understand fungal genetics. Much of this work has focused on elucidating the genetics of biosynthetic gene clusters (BGCs) and the secondary metabolites (SMs) they produce. SMs are both niche defining in fungi and of great economic importance to humans. Despite the focus on A. nidulans, very little is known about the natural diversity in secondary metabolism within this species. We determined the BGC content and looked for evolutionary patterns in BGCs from whole-genome sequences of two clinical isolates and the A4 reference genome of A. nidulans. Differences in BGC content were used to explain SM profiles determined using liquid chromatography-high-resolution mass spectrometry. We found that in addition to genetic variation of BGCs contained by all isolates, nine BGCs varied by presence/absence. We discovered the viridicatumtoxin BGC in A. nidulans and suggest that this BGC has undergone a horizontal gene transfer from the Aspergillus section Nigri lineage into Penicillium sometime after the sections Nigri and Nidulantes diverged. We identified the production of viridicatumtoxin and several other compounds previously not known to be produced by A. nidulans. One isolate showed a lack of sterigmatocystin production even though it contained an apparently intact sterigmatocystin BGC, raising questions about other genes and processes known to regulate this BGC. Altogether, our work uncovers a large degree of intraspecies diversity in BGC and SM production in this genetic model species and offers new avenues to understand the evolution and regulation of secondary metabolism. IMPORTANCE Much of what we know about the genetics underlying secondary metabolite (SM) production and the function of SMs in the model fungus Aspergillus nidulans comes from a single reference genome. A growing body of research indicates the importance of biosynthetic gene cluster (BGC) and SM diversity within a species. However, there is no information about the natural diversity of secondary metabolism in A. nidulans. We discovered six novel clusters that contribute to the considerable variation in both BGC content and SM production within A. nidulans. We characterize a diverse set of mutations and emphasize how findings of single nucleotide polymorphisms (SNPs), deletions, and differences in evolutionary history encompass much of the variation observed in nonmodel systems. Our results emphasize that A. nidulans may also be a strong model to use within-species diversity to elucidate regulatory cross talk, fungal ecology, and drug discovery systems. (AU)

Processo FAPESP: 17/14159-2 - O papel do metabolismo da lactose e do acetato na virulência de Aspergillus fumigatus
Beneficiário:Laure Nicolas Annick Ries
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
Processo FAPESP: 17/19821-5 - Caracterização molecular, fenotípica e da resposta imune de isolados clínicos de Aspergillus nidulans
Beneficiário:Rafael Wesley Bastos
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 19/00631-7 - Caracterização da virulência e da resposta imune de isolados clínicos de Aspergillus nidulans em modelo de infecção em zebrafish
Beneficiário:Rafael Wesley Bastos
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
Processo FAPESP: 16/07870-9 - A influência de proteínas quinases ativadas por mitógenos (MAPK) na expressão de determinantes genéticos importantes para a virulência de Aspergillus fumigatus
Beneficiário:Gustavo Henrique Goldman
Modalidade de apoio: Auxílio à Pesquisa - Temático