Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives.
Aspergillus flavus
aspergillosis
biosynthetic gene cluster
comparative genomics
evolution
fungal keratitis
genomes
genomics
pathogenicity
phenotypic variation
secondary metabolism
secondary metabolites
Journal
Microbiology spectrum
ISSN: 2165-0497
Titre abrégé: Microbiol Spectr
Pays: United States
ID NLM: 101634614
Informations de publication
Date de publication:
21 12 2022
21 12 2022
Historique:
pubmed:
2
11
2022
medline:
28
12
2022
entrez:
1
11
2022
Statut:
ppublish
Résumé
Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus can cause both aspergillosis and fungal keratitis infections, but closely related species are not considered clinically relevant. To study the evolution of A. flavus pathogenicity, we examined genomic and phenotypic traits of two strains of A. flavus and three closely related species, Aspergillus arachidicola (two strains), Aspergillus parasiticus (two strains), and Aspergillus nomiae (one strain). We identified >3,000 orthologous proteins unique to A. flavus, including seven biosynthetic gene clusters present in A. flavus strains and absent in the three nonpathogens. We characterized secondary metabolite production for all seven strains under two clinically relevant conditions, temperature and salt concentration. Temperature impacted metabolite production in all species, whereas salinity did not affect production of any species. Strains of the same species produced different metabolites. Growth under stress conditions revealed additional heterogeneity within species. Using the invertebrate fungal disease model Galleria mellonella, we found virulence of strains of the same species varied widely; A. flavus strains were not more virulent than strains of the nonpathogens. In a murine model of fungal keratitis, we observed significantly lower disease severity and corneal thickness for A. arachidicola compared to other species at 48 h postinfection, but not at 72 h. Our work identifies variations in key phenotypic, chemical, and genomic attributes between A. flavus and its nonpathogenic relatives and reveals extensive strain heterogeneity in virulence that does not correspond to the currently established clinical relevance of these species.
Identifiants
pubmed: 36318036
doi: 10.1128/spectrum.03069-22
pmc: PMC9769809
doi:
Banques de données
figshare
['10.6084/m9.figshare.20256336']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0306922Subventions
Organisme : NEI NIH HHS
ID : F31 EY033235
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY021725
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI153356
Pays : United States
Organisme : NEI NIH HHS
ID : T32 EY023202
Pays : United States
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