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      cAMP-independent signal pathways stimulate hyphal morphogenesis in Candida albicans

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          Summary

          The fungal pathogen Candida albicans can transition from budding to hyphal growth, which promotes biofilm formation and invasive growth into tissues. Stimulation of adenylyl cyclase to form cAMP induces hyphal morphogenesis. The failure of cells lacking adenylyl cyclase ( cyr1Δ) to form hyphae has suggested that cAMP signaling is essential for hyphal growth. However, cyr1Δ mutants also grow slowly and have defects in morphogenesis, making it unclear whether hyphal inducers must stimulate cAMP, or if normal basal levels of cAMP are required to maintain cellular health needed for hyphal growth. Interestingly, supplementation of cyr1Δ cells with low levels of cAMP enabled them to form hyphae in response to the inducer N-acetylglucosamine (GlcNAc), suggesting that a basal level of cAMP is sufficient for stimulation. Furthermore, we isolated faster-growing cyr1Δ pseudorevertant strains that can be induced to form hyphae even though they lack cAMP. The pseudorevertant strains were not induced by CO 2, consistent with reports that CO 2 directly stimulates adenylyl cyclase. Mutational analysis showed that induction of hyphae in a pseudorevertant strain was independent of RAS1, but was dependent on the EFG1 transcription factor that acts downstream of protein kinase A. Thus, cAMP-independent signals contribute to the induction of hyphal responses.

          Abbreviated Summary

          The cAMP signaling pathway induces a switch from budding to hyphal morphogenesis that promotes biofilm formation and invasive growth by the human fungal pathogen Candida albicans. In this study we identified pseudorevertant strains that can form hyphae in the absence of adenylyl cyclase, which indicates that cAMP-independent pathways also contribute to this morphological switch.

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          Author and article information

          Journal
          8712028
          5753
          Mol Microbiol
          Mol. Microbiol.
          Molecular microbiology
          0950-382X
          1365-2958
          6 December 2016
          19 December 2016
          March 2017
          01 March 2018
          : 103
          : 5
          : 764-779
          Affiliations
          [1 ]Department of Molecular Genetics and Microbiology
          [2 ]Graduate Program in Molecular and Cellular Biology
          [3 ]Graduate Program in Molecular Genetics and Microbiology
          Author notes
          [* ]Correspondence to: James B. Konopka, Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5222, USA, Phone: 631-632-8715, Fax: 631-632-9797, james.konopka@ 123456stonybrook.edu
          Article
          PMC5323341 PMC5323341 5323341 nihpa833763
          10.1111/mmi.13588
          5323341
          27888610
          1a457706-d7c7-4607-b21e-e123d1961794
          History
          Categories
          Article

          Candida albicans ,hyphal morphogenesis,adenylyl cyclase,cAMP,pseudorevertants

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