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Developmental regulation of the glyoxylate cycle in the human pathogen Penicillium marneffei

David Cánovas1, Alex Andrianopoulos

  • 1Department of Genetics, University of Melbourne, Vic. 3010, Australia.

Molecular Microbiology
|April 12, 2007
PubMed

Insights

Penicillium marneffei uses the acuD gene for nutrient utilization, with its expression controlled by both temperature and carbon source. This complex regulation, involving AbaA and FacB, likely contributes to the fungus

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Fungal Pathogenesis

Background:

  • Penicillium marneffei is a thermally dimorphic fungus causing opportunistic infections.
  • Pathogenic yeast cells reside intracellularly within macrophages during infection.
  • The glyoxylate cycle is crucial for nutrient acquisition, particularly fatty acids, in many pathogens.

Purpose of the Study:

  • To investigate the role and regulation of the acuD gene, encoding isocitrate lyase, in Penicillium marneffei's utilization of acetate and fatty acids.
  • To elucidate the mechanisms controlling acuD gene expression in response to temperature and carbon availability.
  • To identify regulatory factors involved in the temperature-dependent control of acuD.

Main Methods:

  • Cloning of the P. marneffei acuD gene.
  • Heterologous expression of P. marneffei acuD promoter in Aspergillus nidulans.
  • Heterologous expression of A. nidulans acuD promoter in P. marneffei.
  • Cloning and characterization of the transcriptional activator FacB.
  • Investigating the role of AbaA in acuD regulation through gene deletion.

Main Results:

  • The P. marneffei acuD gene is induced at 37°C, even with repressing carbon sources like glucose.
  • Temperature-dependent regulation of acuD in P. marneffei involves both cis-acting elements and trans-acting factors.
  • FacB mediates carbon source-dependent induction of acuD, but not temperature-dependent induction.
  • AbaA contributes to temperature-dependent acuD induction at 37°C, but is not the sole regulator.

Conclusions:

  • Penicillium marneffei exhibits complex transcriptional regulation of the acuD gene, responding to both carbon source and temperature.
  • The glyoxylate cycle, regulated by acuD, is likely a critical metabolic adaptation for P. marneffei during host infection.
  • A regulatory network involving AbaA and other factors controls acuD expression, potentially contributing to fungal pathogenicity.

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