title: The CRZ1/SP1-like gene links survival under limited aeration, cell integrity and biofilm formation in the pathogenic yeast Cryptococcus neoformans.
abstract: OBJECTIVE
  Limited aeration has been demonstrated to cause slowdown in proliferation and delayed budding, resulting eventually in a unique unbudded G2-arrest in the obligate aerobic pathogenic yeast Cryptococcus neoformans. Also, the ability to adapt to decreased oxygen levels during pathogenesis has been identified as a virulence factor in C. neoformans. The aim of this study was to identify and characterize genes that are necessary for the proliferation slowdown and G2-arrest caused by limited aeration.
  
  
  METHODS
  Random mutants were prepared and screened for lack of typical slowdown of proliferation under limited aeration. The CNAG_00156.2 gene coding for a zinc-finger transcription factor was identified in mutants showing most distinctive phenotype. Targeted deletion strain and reconstituted strain were prepared to characterize and confirm the gene functions. This gene was also identified in a parallel studies as homologous both to calcineurin responsive (Crz1) and PKC1-dependent (SP1-like) transcription factors.
  
  
  RESULTS
  We have confirmed the role of the cryptococcal homologue of CRZ1/SP1-like transcription factor in cell integrity, and newly demonstrated its role in slowdown of proliferation and survival under reduced aeration, in biofilm formation and in susceptibility to fluconazole.
  
  
  CONCLUSIONS
  Our data demonstrate a tight molecular link between slowdown of proliferation during hypoxic adaptation and maintenance of cell integrity in C. neoformans and present a new role for the CRZ1 family of transcription factors in fungi. The exact positioning of this protein in cryptococcal signalling cascades remains to be clarified.
authors: Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.
authors: Zuzana
authors: Z
authors: Moranova
authors: Eric
authors: E
authors: Virtudazo
authors: Kristyna
authors: K
authors: Hricova
authors: Misako
authors: M
authors: Ohkusu
authors: Susumu
authors: S
authors: Kawamoto
authors: Vendula
authors: V
authors: Husickova
authors: Vladislav
authors: V
authors: Raclavsky
mesh_terms: D000693:Anaerobiosis; D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development*; D015725:Fluconazole / Q000494:pharmacology; D017353:Gene Deletion; D050296:Microbial Viability; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000935:Antifungal Agents; D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; D015725:Fluconazole