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

Caroline S. Meier, Marco Pagni, Sophie Richard, Konrad Mühlethaler, João M. G. C. F. Almeida, Gilles Nevez, Melanie T. Cushion, Enrique J. Calderón and Philippe M. Hauser ()
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Caroline S. Meier: Lausanne University Hospital and University of Lausanne
Marco Pagni: SIB Swiss Institute of Bioinformatics
Sophie Richard: Lausanne University Hospital and University of Lausanne
Konrad Mühlethaler: University of Bern
João M. G. C. F. Almeida: Universidade NOVA de Lisboa
Gilles Nevez: Laboratoire de Parasitologie et Mycologie, Hôpital de La Cavale Blanche, CHU de Brest
Melanie T. Cushion: University of Cincinnati
Enrique J. Calderón: Hospital Universitario Virgen del Rocίo/Consejo Superior de Investigaciones Cientίficas/Universidad de Sevilla
Philippe M. Hauser: Lausanne University Hospital and University of Lausanne

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms. Understanding these mechanisms is important to better prevent and fight the deadly diseases caused. Those used by the fungus Pneumocystis jirovecii that causes life-threatening pneumonia in immunocompromised individuals remain poorly understood. Here, though this fungus is currently not cultivable, our detailed analysis of the subtelomeric sequence motifs and genes encoding surface proteins suggests that the system involves the reassortment of the repertoire of ca. 80 non-expressed genes present in each strain, from which single genes are retrieved for mutually exclusive expression. Dispersion of the new repertoires, supposedly by healthy carrier individuals, appears very efficient because identical alleles are observed in patients from different countries. Our observations reveal a unique strategy of antigenic variation. They also highlight the possible role in genome rearrangements of small imperfect mirror sequences forming DNA triplexes.

Date: 2023
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DOI: 10.1038/s41467-023-42685-6

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