Characterisation of the heat shock factor of the human thermodimorphic pathogen Paracoccidioides lutzii

Hugo Costa Paes1, Thiago Machado Mello-de-Sousa, Larissa Fernandes

  • 1Departamento de Biologia Celular, Universidade de Brasília, 70910-900 Brasília, DF, Brazil.

Insights

Heat shock factor (Hsf) may regulate the temperature-dependent yeast-to-mould transition in thermodimorphic fungi. This study characterizes the Hsf from Paracoccidioides lutzii, revealing its unique domains and regulatory interactions.

Area of Science:

  • Mycology
  • Molecular Biology
  • Fungal Pathogenesis

Background:

  • Thermodimorphic fungi cause systemic mycoses, exhibiting a unique ability to switch between mould and yeast forms based on temperature.
  • The molecular mechanisms governing this thermal transition are not fully understood.
  • Heat shock factor (Hsf), Drk1, and Ryp proteins are known regulators of cellular responses to thermal stress.

Purpose of the Study:

  • To investigate the potential role of heat shock factor (Hsf) in the thermodimorphism of Paracoccidioides lutzii.
  • To characterize the Hsf from P. lutzii and its functional domains.
  • To explore the evolutionary significance and regulatory interactions of PlHsf.

Main Methods:

  • Characterization of the heat shock factor (Hsf) from Paracoccidioides lutzii (PlHsf).
  • Functional analysis of PlHsf in Saccharomyces cerevisiae to assess its ability to rescue protein loss.
  • In silico analysis of PlHsf DNA-binding domain interactions with promoter regions of known regulatory genes.
  • In silico screening for heat shock elements in P. lutzii open reading frames (ORFs).

Main Results:

  • PlHsf exhibits regulatory domains unique to the Eurotiomycetidae family, indicating evolutionary specialization.
  • PlHsf successfully rescued the lethal phenotype of Hsf-deficient Saccharomyces cerevisiae.
  • The DNA-binding domain of PlHsf recognized regulatory elements in the promoters of Drk1 and Ryp1.
  • A significant percentage (7%) of P. lutzii ORFs possess a heat shock element in their upstream sequences.

Conclusions:

  • This study provides the first description of a heat shock factor in a thermodimorphic fungus.
  • PlHsf is a potential key regulator in the temperature-dependent morphological transition of Paracoccidioides lutzii.
  • The findings suggest a conserved role for Hsf in fungal thermodimorphism and highlight evolutionary adaptations.

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