TY - JOUR
T1 - Fungal antigenic variation using mosaicism and reassortment of subtelomeric genes’ repertoires
AU - Meier, Caroline S.
AU - Pagni, Marco
AU - Richard, Sophie
AU - Mühlethaler, Konrad
AU - Almeida, João M. G. C. F.
AU - Nevez, Gilles
AU - Cushion, Melanie T.
AU - Calderón, Enrique J.
AU - Hauser, Philippe M.
N1 - Funding Information:
The present work was submitted by C.S.M. as partial fulfillment of a Ph.D. degree at the Faculty of Biology and Medicine of the University of Lausanne. Sequencing was performed at the Lausanne Genomic Technologies Facility, University of Lausanne. We thank Patrick Taffé (Unisanté, Division of Biostatistics, University of Lausanne) for input into the simulation experiments. This work was supported by Swiss National Science Foundation grant 310030_192802 to P.M.H. The Swiss National Science Foundation had no role in any steps of the study. M.T.C. is a Senior Research Career Scientist supported by IK6BX005232 Department of Veterans Affairs. All materials are available from the corresponding author.
Funding Information:
The present work was submitted by C.S.M. as partial fulfillment of a Ph.D. degree at the Faculty of Biology and Medicine of the University of Lausanne. Sequencing was performed at the Lausanne Genomic Technologies Facility, University of Lausanne. We thank Patrick Taffé (Unisanté, Division of Biostatistics, University of Lausanne) for input into the simulation experiments. This work was supported by Swiss National Science Foundation grant 310030_192802 to P.M.H. The Swiss National Science Foundation had no role in any steps of the study. M.T.C. is a Senior Research Career Scientist supported by IK6BX005232 Department of Veterans Affairs. All materials are available from the corresponding author.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85175728722&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-42685-6
DO - 10.1038/s41467-023-42685-6
M3 - Article
C2 - 37919276
AN - SCOPUS:85175728722
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7026
ER -
