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Fungal antigenic variation using mosaicism and reassortment of subtelomeric genes' repertoires

Caroline S Meier1, Marco Pagni2, Sophie Richard1

  • 1Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Nature Communications
|November 3, 2023
PubMed

Insights

Pneumocystis jirovecii uses a unique antigenic variation strategy by shuffling surface protein genes. This helps the fungus evade immune responses, causing pneumonia in immunocompromised patients.

Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Surface antigenic variation is a key survival mechanism for human pathogens.
  • Pneumocystis jirovecii causes severe pneumonia, particularly in immunocompromised individuals.
  • The antigenic variation mechanisms of P. jirovecii are not well understood.

Purpose of the Study:

  • To elucidate the antigenic variation system employed by Pneumocystis jirovecii.
  • To understand how P. jirovecii evades the host immune system.

Main Methods:

  • Detailed analysis of subtelomeric sequence motifs.
  • Examination of genes encoding surface proteins.
  • Bioinformatic analysis of gene repertoires and expression.

Main Results:

  • P. jirovecii appears to utilize a repertoire of approximately 80 non-expressed surface protein genes.
  • Single genes are selected for mutually exclusive expression, creating variation.
  • Efficient dispersion of new gene repertoires is suggested by identical alleles found globally.

Conclusions:

  • P. jirovecii exhibits a unique strategy for surface antigenic variation.
  • Small imperfect mirror sequences forming DNA triplexes may play a role in genome rearrangements.
  • Understanding this system is crucial for combating P. jirovecii infections.

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