1887

Abstract

is an important human fungal pathogen that also serves as a model for studies of fungal pathogenesis. contains several genes encoding peptidyl-prolyl / 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 , which is believed to be the first (and probably only) parvulin-class PPIase in . It is shown that from is structurally and functionally homologous to from , which encodes an essential PPIase that interacts with RNA polymerase II and plays a role in transcription. In , was found to be dispensable for growth, haploid fruiting and capsule formation. However, 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 mutants, or to defects in transcription of as-yet-unidentified virulence genes. The fact that Ess1 is not essential in 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 mutants were hypersensitive to cyclosporin A. might therefore be a useful organism in which to investigate crosstalk among different families of prolyl isomerases.

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2005-05-01
2024-03-29
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