Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans.
The fungal pathogen Candida albicans is a common cause of opportunistic infections in humans. We report that wild-type Drosophila melanogaster (OrR) flies are susceptible to virulent C. albicans infections and have established experimental conditions that enable OrR flies to serve as model hosts for...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3215725?pdf=render |
| _version_ | 1818246322333941760 |
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| author | Monica M Davis Francisco J Alvarez Kicki Ryman Åsa A Holm Per O Ljungdahl Ylva Engström |
| author_facet | Monica M Davis Francisco J Alvarez Kicki Ryman Åsa A Holm Per O Ljungdahl Ylva Engström |
| author_sort | Monica M Davis |
| collection | DOAJ |
| description | The fungal pathogen Candida albicans is a common cause of opportunistic infections in humans. We report that wild-type Drosophila melanogaster (OrR) flies are susceptible to virulent C. albicans infections and have established experimental conditions that enable OrR flies to serve as model hosts for studying C. albicans virulence. After injection into the thorax, wild-type C. albicans cells disseminate and invade tissues throughout the fly, leading to lethality. Similar to results obtained monitoring systemic infections in mice, well-characterized cph1Δ efg1Δ and csh3Δ fungal mutants exhibit attenuated virulence in flies. Using the OrR fly host model, we assessed the virulence of C. albicans strains individually lacking functional components of the SPS sensing pathway. In response to extracellular amino acids, the plasma membrane localized SPS-sensor (Ssy1, Ptr3, and Ssy5) activates two transcription factors (Stp1 and Stp2) to differentially control two distinct modes of nitrogen acquisition (host protein catabolism and amino acid uptake, respectively). Our results indicate that a functional SPS-sensor and Stp1 controlled genes required for host protein catabolism and utilization, including the major secreted aspartyl protease SAP2, are required to establish virulent infections. By contrast, Stp2, which activates genes required for amino acid uptake, is dispensable for virulence. These results indicate that nutrient availability within infected hosts directly influences C. albicans virulence. |
| first_indexed | 2024-12-12T14:46:58Z |
| format | Article |
| id | doaj.art-19c159a47888420083ba513790ea7d84 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T14:46:58Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-19c159a47888420083ba513790ea7d842022-12-22T00:21:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2743410.1371/journal.pone.0027434Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans.Monica M DavisFrancisco J AlvarezKicki RymanÅsa A HolmPer O LjungdahlYlva EngströmThe fungal pathogen Candida albicans is a common cause of opportunistic infections in humans. We report that wild-type Drosophila melanogaster (OrR) flies are susceptible to virulent C. albicans infections and have established experimental conditions that enable OrR flies to serve as model hosts for studying C. albicans virulence. After injection into the thorax, wild-type C. albicans cells disseminate and invade tissues throughout the fly, leading to lethality. Similar to results obtained monitoring systemic infections in mice, well-characterized cph1Δ efg1Δ and csh3Δ fungal mutants exhibit attenuated virulence in flies. Using the OrR fly host model, we assessed the virulence of C. albicans strains individually lacking functional components of the SPS sensing pathway. In response to extracellular amino acids, the plasma membrane localized SPS-sensor (Ssy1, Ptr3, and Ssy5) activates two transcription factors (Stp1 and Stp2) to differentially control two distinct modes of nitrogen acquisition (host protein catabolism and amino acid uptake, respectively). Our results indicate that a functional SPS-sensor and Stp1 controlled genes required for host protein catabolism and utilization, including the major secreted aspartyl protease SAP2, are required to establish virulent infections. By contrast, Stp2, which activates genes required for amino acid uptake, is dispensable for virulence. These results indicate that nutrient availability within infected hosts directly influences C. albicans virulence.http://europepmc.org/articles/PMC3215725?pdf=render |
| spellingShingle | Monica M Davis Francisco J Alvarez Kicki Ryman Åsa A Holm Per O Ljungdahl Ylva Engström Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans. PLoS ONE |
| title | Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans. |
| title_full | Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans. |
| title_fullStr | Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans. |
| title_full_unstemmed | Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans. |
| title_short | Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans. |
| title_sort | wild type drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of candida albicans |
| url | http://europepmc.org/articles/PMC3215725?pdf=render |
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