Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants
Abstract Background Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysac...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | BMC Microbiology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12866-021-02410-z |
| _version_ | 1819009298744737792 |
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| author | B. Ball E. Woroszchuk A. Sukumaran H. West A. Afaq D. Carruthers-Lay B. Muselius L. Gee M. Langille S. Pladwig S. Kazi A. Hendriks J. Geddes-McAlister |
| author_facet | B. Ball E. Woroszchuk A. Sukumaran H. West A. Afaq D. Carruthers-Lay B. Muselius L. Gee M. Langille S. Pladwig S. Kazi A. Hendriks J. Geddes-McAlister |
| author_sort | B. Ball |
| collection | DOAJ |
| description | Abstract Background Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival. Results Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions. Conclusions Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants. |
| first_indexed | 2024-12-21T00:54:09Z |
| format | Article |
| id | doaj.art-d6f3bef5e3bf423ebc15df5df1497892 |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-21T00:54:09Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj.art-d6f3bef5e3bf423ebc15df5df14978922022-12-21T19:21:21ZengBMCBMC Microbiology1471-21802021-12-0121111610.1186/s12866-021-02410-zProteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinantsB. Ball0E. Woroszchuk1A. Sukumaran2H. West3A. Afaq4D. Carruthers-Lay5B. Muselius6L. Gee7M. Langille8S. Pladwig9S. Kazi10A. Hendriks11J. Geddes-McAlister12Department of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphAbstract Background Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival. Results Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions. Conclusions Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants.https://doi.org/10.1186/s12866-021-02410-zCryptococcus neoformansFungal pathogenesisZinc limitationQuantitative proteomicsPolysaccharide capsuleVirulence |
| spellingShingle | B. Ball E. Woroszchuk A. Sukumaran H. West A. Afaq D. Carruthers-Lay B. Muselius L. Gee M. Langille S. Pladwig S. Kazi A. Hendriks J. Geddes-McAlister Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants BMC Microbiology Cryptococcus neoformans Fungal pathogenesis Zinc limitation Quantitative proteomics Polysaccharide capsule Virulence |
| title | Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants |
| title_full | Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants |
| title_fullStr | Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants |
| title_full_unstemmed | Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants |
| title_short | Proteome and secretome profiling of zinc availability in Cryptococcus neoformans identifies Wos2 as a subtle influencer of fungal virulence determinants |
| title_sort | proteome and secretome profiling of zinc availability in cryptococcus neoformans identifies wos2 as a subtle influencer of fungal virulence determinants |
| topic | Cryptococcus neoformans Fungal pathogenesis Zinc limitation Quantitative proteomics Polysaccharide capsule Virulence |
| url | https://doi.org/10.1186/s12866-021-02410-z |
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