Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives
ABSTRACT 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 pat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.03069-22 |
| _version_ | 1811195042656681984 |
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| author | E. Anne Hatmaker Manuel Rangel-Grimaldo Huzefa A. Raja Hadi Pourhadi Sonja L. Knowles Kevin Fuller Emily M. Adams Jorge D. Lightfoot Rafael W. Bastos Gustavo H. Goldman Nicholas H. Oberlies Antonis Rokas |
| author_facet | E. Anne Hatmaker Manuel Rangel-Grimaldo Huzefa A. Raja Hadi Pourhadi Sonja L. Knowles Kevin Fuller Emily M. Adams Jorge D. Lightfoot Rafael W. Bastos Gustavo H. Goldman Nicholas H. Oberlies Antonis Rokas |
| author_sort | E. Anne Hatmaker |
| collection | DOAJ |
| description | ABSTRACT 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. IMPORTANCE Aspergillus flavus is a filamentous fungus that causes opportunistic human infections, such as aspergillosis and fungal keratitis, but its close relatives are considered nonpathogenic. To begin understanding how this difference in pathogenicity evolved, we characterized variation in infection-relevant genomic, chemical, and phenotypic traits between strains of A. flavus and its relatives. We found extensive variation (or strain heterogeneity) within the pathogenic A. flavus as well as within its close relatives, suggesting that strain-level differences may play a major role in the ability of these fungi to cause disease. Surprisingly, we also found that the virulence of strains from species not considered to be pathogens was similar to that of A. flavus in both invertebrate and murine models of disease. These results contrast with previous studies on Aspergillus fumigatus, another major pathogen in the genus, for which significant differences in infection-relevant chemical and phenotypic traits are observed between closely related pathogenic and nonpathogenic species. |
| first_indexed | 2024-04-12T00:37:07Z |
| format | Article |
| id | doaj.art-27eea169c6a54f3c975c28609b6cd361 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-12T00:37:07Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-27eea169c6a54f3c975c28609b6cd3612022-12-22T03:55:08ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-12-0110610.1128/spectrum.03069-22Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close RelativesE. Anne Hatmaker0Manuel Rangel-Grimaldo1Huzefa A. Raja2Hadi Pourhadi3Sonja L. Knowles4Kevin Fuller5Emily M. Adams6Jorge D. Lightfoot7Rafael W. Bastos8Gustavo H. Goldman9Nicholas H. Oberlies10Antonis Rokas11Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USADepartment of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USADepartment of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USADepartment of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USADepartment of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USADepartment of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USADepartment of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USADepartment of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USABiosciences Center, Federal University of Rio Grande do Norte, Natal, BrazilFaculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, BrazilDepartment of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USADepartment of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USAABSTRACT 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. IMPORTANCE Aspergillus flavus is a filamentous fungus that causes opportunistic human infections, such as aspergillosis and fungal keratitis, but its close relatives are considered nonpathogenic. To begin understanding how this difference in pathogenicity evolved, we characterized variation in infection-relevant genomic, chemical, and phenotypic traits between strains of A. flavus and its relatives. We found extensive variation (or strain heterogeneity) within the pathogenic A. flavus as well as within its close relatives, suggesting that strain-level differences may play a major role in the ability of these fungi to cause disease. Surprisingly, we also found that the virulence of strains from species not considered to be pathogens was similar to that of A. flavus in both invertebrate and murine models of disease. These results contrast with previous studies on Aspergillus fumigatus, another major pathogen in the genus, for which significant differences in infection-relevant chemical and phenotypic traits are observed between closely related pathogenic and nonpathogenic species.https://journals.asm.org/doi/10.1128/spectrum.03069-22Aspergillus flavusgenomesphenotypic variationsecondary metabolitesfungal keratitisaspergillosis |
| spellingShingle | E. Anne Hatmaker Manuel Rangel-Grimaldo Huzefa A. Raja Hadi Pourhadi Sonja L. Knowles Kevin Fuller Emily M. Adams Jorge D. Lightfoot Rafael W. Bastos Gustavo H. Goldman Nicholas H. Oberlies Antonis Rokas Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives Microbiology Spectrum Aspergillus flavus genomes phenotypic variation secondary metabolites fungal keratitis aspergillosis |
| title | Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives |
| title_full | Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives |
| title_fullStr | Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives |
| title_full_unstemmed | Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives |
| title_short | Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives |
| title_sort | genomic and phenotypic trait variation of the opportunistic human pathogen aspergillus flavus and its close relatives |
| topic | Aspergillus flavus genomes phenotypic variation secondary metabolites fungal keratitis aspergillosis |
| url | https://journals.asm.org/doi/10.1128/spectrum.03069-22 |
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