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Sterol biosynthesis and sterol uptake in the fungal pathogen Pneumocystis carinii

Tiffany M Joffrion1, Melanie T Cushion

  • 1Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA. joffritm@mail.uc.edu

FEMS Microbiology Letters
|June 10, 2010
PubMed

Insights

Pneumocystis fungi, often causing pneumonia in immunocompromised individuals, possess unique sterol biosynthesis pathways. Research reveals these fungi utilize cholesterol and have functional genes for sterol synthesis, impacting antifungal drug resistance.

Area of Science:

  • Mycology
  • Medical Mycology
  • Fungal Pathogenesis

Background:

  • Pneumocystis species are fungi that colonize mammals, causing Pneumocystis pneumonia in immunocompromised hosts.
  • These fungi are atypical, utilizing cholesterol instead of ergosterol and scavenging sterols from hosts.
  • This sterol utilization has historically suggested resistance to ergosterol-targeting antifungal drugs.

Purpose of the Study:

  • To investigate the sterol biosynthesis pathways in Pneumocystis species.
  • To understand the mechanisms of sterol scavenging and their implications for antifungal drug resistance.
  • To determine the functionality of sterol biosynthetic genes in Pneumocystis carinii.

Main Methods:

  • Genome scans to identify sterol biosynthetic genes in Pneumocystis carinii.
  • In vitro assays to assess the functionality of these genes.
  • Heterologous expression of Pneumocystis carinii sterol genes.
  • Biochemical analyses of lipid content in Pneumocystis carinii cellular membranes.

Main Results:

  • Genome scans and in vitro assays confirmed the presence and functionality of sterol biosynthetic genes in Pneumocystis carinii.
  • Targeted inhibition of these enzymes led to reduced viability of Pneumocystis carinii.
  • Biochemical analyses provided insights into both sterol biosynthesis and scavenging mechanisms.

Conclusions:

  • Pneumocystis carinii possesses functional sterol biosynthesis pathways, contrary to previous assumptions.
  • These findings challenge the notion that Pneumocystis are inherently resistant to all antifungal drugs.
  • Understanding these pathways is crucial for developing new therapeutic strategies against Pneumocystis pneumonia.

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