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S-adenosylmethionine and Pneumocystis carinii

S Merali1, D Vargas, M Franklin

  • 1Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10010, USA. merals01@popmail.med.nyu.edu

The Journal of Biological Chemistry
|May 16, 2000
PubMed

Insights

Pneumocystis carinii, an opportunistic fungal pathogen, absolutely requires S-adenosylmethionine (AdoMet) for growth. This study reveals P. carinii is an AdoMet auxotroph, making its uptake a target for new therapies.

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Biochemistry

Background:

  • Pneumocystis carinii is an opportunistic fungal pathogen associated with AIDS.
  • S-adenosylmethionine (AdoMet) is crucial for methylation and polyamine biosynthesis.
  • Previous work showed AdoMet enhances P. carinii axenic culture.

Purpose of the Study:

  • To determine if AdoMet is essential for P. carinii continuous growth.
  • To characterize the AdoMet uptake mechanism in P. carinii.
  • To investigate potential chemotherapeutic targets related to AdoMet metabolism.

Main Methods:

  • Axenic culture of P. carinii.
  • Characterization of AdoMet transporters (affinity, pH optimum, competitive inhibition).
  • Assessment of AdoMet uptake under various conditions (temperature, inhibitors).
  • Measurement of AdoMet synthetase activity.
  • Correlation analysis between rat AdoMet levels and P. carinii burden.

Main Results:

  • AdoMet is absolutely required for continuous P. carinii growth.
  • Two AdoMet transporters were identified: high-affinity (K(m)=4.5 µM) and low-affinity (K(m)=333 µM).
  • High-affinity transport is active, pH-dependent (optimum 7.5), and relies on cytochrome and alternative oxidase pathways.
  • P. carinii lacks detectable AdoMet synthetase activity.
  • Rat AdoMet plasma concentration inversely correlates with lung P. carinii load.

Conclusions:

  • Pneumocystis carinii is an S-adenosylmethionine (AdoMet) auxotroph.
  • The characterized AdoMet uptake system represents a promising target for novel chemotherapeutic strategies against P. carinii infections.

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