Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans.
Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faste...
| Main Authors: | , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado: |
Public Library of Science (PLoS)
2021-08-01
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| Series: | PLoS Pathogens |
| Acceso en liña: | https://doi.org/10.1371/journal.ppat.1009861 |
| _version_ | 1828902299684044800 |
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| author | Kyunghun Min Thomas F Jannace Haoyu Si Krishna R Veeramah John D Haley James B Konopka |
| author_facet | Kyunghun Min Thomas F Jannace Haoyu Si Krishna R Veeramah John D Haley James B Konopka |
| author_sort | Kyunghun Min |
| collection | DOAJ |
| description | Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1Δ/Δ pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase A (PKA) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of adenylyl cyclase is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis. |
| first_indexed | 2024-12-13T16:15:34Z |
| format | Article |
| id | doaj.art-bae2262ee94e452f978d20bae7de2977 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T16:15:34Z |
| publishDate | 2021-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-bae2262ee94e452f978d20bae7de29772022-12-21T23:38:51ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-08-01178e100986110.1371/journal.ppat.1009861Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans.Kyunghun MinThomas F JannaceHaoyu SiKrishna R VeeramahJohn D HaleyJames B KonopkaMicrobial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1Δ/Δ pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase A (PKA) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of adenylyl cyclase is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis.https://doi.org/10.1371/journal.ppat.1009861 |
| spellingShingle | Kyunghun Min Thomas F Jannace Haoyu Si Krishna R Veeramah John D Haley James B Konopka Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans. PLoS Pathogens |
| title | Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans. |
| title_full | Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans. |
| title_fullStr | Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans. |
| title_full_unstemmed | Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans. |
| title_short | Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans. |
| title_sort | integrative multi omics profiling reveals camp independent mechanisms regulating hyphal morphogenesis in candida albicans |
| url | https://doi.org/10.1371/journal.ppat.1009861 |
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