Authors

P Hauser¹;  ¹ Centre Hospitalier Universitaire Vaudois, Switzerland

Discussion

Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms to modify or exchange the protein that is exposed on the cell surface, at the genetic, expressional, and/or epigenetic level. We studied those used by the fungus Pneumocystis jirovecii that causes life-threatening pneumonia in immunocompromised individuals. Though this fungus is currently not cultivable, our detailed analysis of the subtelomeric sequence motifs and genes encoding six families of major surface glycoproteins suggests that the system involves homologous recombinations. Translocations of entire genes lead to the reassortment of the repertoire of ca. 80 non-expressed alleles of family I present in each strain, from which single genes are retrieved over time for mutually exclusive expression within subpopulations of cells. The recombinations also lead to allele mosaicism and rearrangement of the subtelomeres. In addition, imperfect mirror sequences forming DNA triplexes are likely to play a role in the system