The Ess1 prolyl isomerase is dispensable for growth but required for virulence in Cryptococcus neoformans.
Cryptococcus neoformans is an important human fungal pathogen that also serves as a model for studies of fungal pathogenesis. C. neoformans contains several genes encoding peptidyl-prolyl cis/trans isomerases (PPIases), enzymes that catalyse changes in the folding and conformation of target proteins. Three distinct classes of PPIases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. This paper reports the cloning and characterization of ESS1, which is believed to be the first (and probably only) parvulin-class PPIase in C. neoformans. It is shown that ESS1 from C. neoformans is structurally and functionally homologous to ESS1 from Saccharomyces cerevisiae, which encodes an essential PPIase that interacts with RNA polymerase II and plays a role in transcription. In C. neoformans, ESS1 was found to be dispensable for growth, haploid fruiting and capsule formation. However, ESS1 was required for virulence in a murine model of cryptococcosis. Loss of virulence might have been due to the defects in melanin and urease production observed in ess1 mutants, or to defects in transcription of as-yet-unidentified virulence genes. The fact that Ess1 is not essential in C. neoformans suggests that, in this organism, some of its functions might be subsumed by other prolyl isomerases, in particular, cyclophilins Cpa1 or Cpa2. This is supported by the finding that ess1 mutants were hypersensitive to cyclosporin A. C. neoformans might therefore be a useful organism in which to investigate crosstalk among different families of prolyl isomerases.
Ren
Ping
P
Mycology Laboratory, Wadsworth Center, New York State Department of Health, State University of New York, Albany, NY 12208, USA.|Molecular Genetics Program, Wadsworth Center, New York State Department of Health, State University of New York, Albany, NY 12208, USA.
Rossettini
Anne
A
Molecular Genetics Program, Wadsworth Center, New York State Department of Health, State University of New York, Albany, NY 12208, USA.
Chaturvedi
Vishnu
V
Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, NY 12208, USA.|Mycology Laboratory, Wadsworth Center, New York State Department of Health, State University of New York, Albany, NY 12208, USA.|Molecular Genetics Program, Wadsworth Center, New York State Department of Health, State University of New York, Albany, NY 12208, USA.
Hanes
Steven D
SD
Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, NY 12208, USA.|Molecular Genetics Program, Wadsworth Center, New York State Department of Health, State University of New York, Albany, NY 12208, USA.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003455:Cryptococcus neoformans / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000382:microbiology / Q000401:mortality*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D014774:Virulence
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D029701:Saccharomyces cerevisiae Proteins; C000606845:ESS1 protein, S cerevisiae; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse