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

Caroline S Meier (1) , Marco Pagni (2) , Sophie Richard (1) , Konrad Mühlethaler , João M G C F Almeida (3) , Gilles Nevez (4, 5, 6, 7) , Melanie T Cushion (8) , Enrique J Calderón (9) , Philippe M Hauser (10, 1)

1 LBTI - Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305
2 SIB - Swiss Institute of Bioinformatics [Lausanne]
3 Instituto de Telecomunicações [Lisboa, Portugal]
4 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
5 UBO - Université de Brest
6 UA - Université d'Angers
7 IRF - Infections Respiratoires Fongiques
8 UC - University of Cincinnati
9 Hospital Universitario Virgen del Rocío [Sevilla]
10 UNIL - Université de Lausanne = University of Lausanne

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.

Domaines: Mycologie

Caroline S Meier, Marco Pagni, Sophie Richard, Konrad Mühlethaler, João M G C F Almeida, et al.. Fungal antigenic variation using mosaicism and reassortment of subtelomeric genes’ repertoires. Nature Communications, 2023, 14, pp.7026. ⟨10.1038/s41467-023-42685-6⟩. ⟨hal-04302223⟩