Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeasts
The dimorphic fungus Histoplasma capsulatum, which almost exclusively resides within host phagocytic cells during infection, must meet its nutritional needs by scavenging molecules from the phagosome environment. The requirement for gluconeogenesis, but not fatty acid catabolism, for intracellular g...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2024.2438750 |
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| author | Stephanie C. Ray Qian Shen Chad A. Rappleye |
| author_facet | Stephanie C. Ray Qian Shen Chad A. Rappleye |
| author_sort | Stephanie C. Ray |
| collection | DOAJ |
| description | The dimorphic fungus Histoplasma capsulatum, which almost exclusively resides within host phagocytic cells during infection, must meet its nutritional needs by scavenging molecules from the phagosome environment. The requirement for gluconeogenesis, but not fatty acid catabolism, for intracellular growth, implicates amino acids as a likely intracellular nutrient source. Consequently, we investigated Histoplasma growth on amino acids. Growth assays demonstrated that Histoplasma yeasts readily utilize most amino acids as nitrogen sources but only efficiently catabolize glutamine, glutamate, aspartate, proline, isoleucine, and alanine as carbon sources. An amino acid permease-based conserved domain search identified 28 putative amino acid transporters within the Histoplasma genome. We characterized the substrate specificities of the major Histoplasma amino acid transporters using a Saccharomyces cerevisiae heterologous expression system and found that H. capsulatum Dip5, Gap3, and a newly described permease, Gai1, comprise most of Histoplasma’s amino acid import capacity. Histoplasma yeasts deficient in these three transporters are impaired for growth on free amino acids but proliferate within macrophages and remain fully virulent during infection of mice, indicating that free amino acids are not the principal nutrient source within the phagosome to support Histoplasma proliferation during infection. |
| format | Article |
| id | doaj-art-7752bca5725d4d28a4960aafa13e3d4a |
| institution | Kabale University |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-7752bca5725d4d28a4960aafa13e3d4a2024-12-09T18:44:40ZengTaylor & Francis GroupVirulence2150-55942150-56082024-12-0115110.1080/21505594.2024.2438750Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeastsStephanie C. Ray0Qian Shen1Chad A. Rappleye2Department of Microbiology, Ohio State University, Columbus, OH, USADepartment of Biology, Rhodes College, Memphis, TN, USADepartment of Microbiology, Ohio State University, Columbus, OH, USAThe dimorphic fungus Histoplasma capsulatum, which almost exclusively resides within host phagocytic cells during infection, must meet its nutritional needs by scavenging molecules from the phagosome environment. The requirement for gluconeogenesis, but not fatty acid catabolism, for intracellular growth, implicates amino acids as a likely intracellular nutrient source. Consequently, we investigated Histoplasma growth on amino acids. Growth assays demonstrated that Histoplasma yeasts readily utilize most amino acids as nitrogen sources but only efficiently catabolize glutamine, glutamate, aspartate, proline, isoleucine, and alanine as carbon sources. An amino acid permease-based conserved domain search identified 28 putative amino acid transporters within the Histoplasma genome. We characterized the substrate specificities of the major Histoplasma amino acid transporters using a Saccharomyces cerevisiae heterologous expression system and found that H. capsulatum Dip5, Gap3, and a newly described permease, Gai1, comprise most of Histoplasma’s amino acid import capacity. Histoplasma yeasts deficient in these three transporters are impaired for growth on free amino acids but proliferate within macrophages and remain fully virulent during infection of mice, indicating that free amino acids are not the principal nutrient source within the phagosome to support Histoplasma proliferation during infection.https://www.tandfonline.com/doi/10.1080/21505594.2024.2438750Histoplasmapathogenesisphagosomeamino acid transportermacrophage |
| spellingShingle | Stephanie C. Ray Qian Shen Chad A. Rappleye Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeasts Virulence Histoplasma pathogenesis phagosome amino acid transporter macrophage |
| title | Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeasts |
| title_full | Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeasts |
| title_fullStr | Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeasts |
| title_full_unstemmed | Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeasts |
| title_short | Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeasts |
| title_sort | three transporters including the novel gai1 permease drive amino acid uptake in histoplasma yeasts |
| topic | Histoplasma pathogenesis phagosome amino acid transporter macrophage |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2024.2438750 |
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