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Published on: February 23, 2014
Variation in the major surface glycoprotein genes in Pneumocystis jirovecii
Geetha Kutty1, Frank Maldarelli, Guillaume Achaz
1Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
The genome of Pneumocystis, which causes life-threatening pneumonia in immunosuppressed patients, contains a multicopy gene family that encodes the major surface glycoprotein (Msg). Pneumocystis can vary the expressed Msg, presumably as a mechanism to avoid host immune responses. Analysis of 24 msg-gene sequences obtained from a single human isolate of Pneumocystis demonstrated that the sequences segregate into 2 branches. Results of a number of analyses suggest that recombination between msg genes is an important mechanism for generating msg diversity. Intrabranch recombination occurred more frequently than interbranch recombination. Restriction-fragment length polymorphism analysis of human isolates of Pneumocystis demonstrated substantial variation in the repertoire of the msg-gene family, variation that was not observed in laboratory isolates of Pneumocystis in rats or mice; this may be the result of examining outbred versus captive populations. Increased diversity in the Msg repertoire, generated in part by recombination, increases the potential for antigenic variation in this abundant surface protein.
Insights
Pneumocystis pneumonia (PCP) relies on major surface glycoprotein (Msg) gene diversity for immune evasion. Recombination between Msg genes generates this diversity, enabling antigenic variation in Pneumocystis.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Pneumocystis causes life-threatening pneumonia in immunosuppressed individuals.
- The Pneumocystis genome features a multicopy gene family encoding the major surface glycoprotein (Msg).
- Pneumocystis likely varies expressed Msg to evade host immune responses.
Purpose of the Study:
- To investigate the mechanisms generating diversity in the Msg gene family.
- To understand the role of recombination in Msg gene evolution.
- To analyze variations in the Msg gene repertoire across different Pneumocystis isolates.
Main Methods:
- Sequencing of 24 msg-gene sequences from a human Pneumocystis isolate.
- Analysis of gene sequence segregation into distinct branches.
- Restriction-fragment length polymorphism (RFLP) analysis of human and laboratory Pneumocystis isolates.
Main Results:
- Msg gene sequences segregated into two main branches.
- Recombination between msg genes was identified as a key driver of msg diversity.
- Intrabranch recombination was more frequent than interbranch recombination.
- Human Pneumocystis isolates exhibited significant variation in the msg-gene family repertoire compared to laboratory isolates.
Conclusions:
- Recombination is a crucial mechanism for generating msg diversity in Pneumocystis.
- Increased Msg repertoire diversity enhances the potential for antigenic variation.
- Differences in observed variation may relate to outbred human populations versus captive animal models.
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