A study led by a team of researchers from the Institute of Microbiology of CHUV-UNIL and SIB Swiss Institute of Bioinformatics reveals the mechanisms of antigenic variation used by the pathogen Pneumocystis jirovecii to escape the human immune system. Published in mBio, the paper was featured in a recent podcast by 'This week in microbiology'.
P. jirovecii asci stained with silver (Institute of Microbiology, CHUV Hospital)
Pneumocystis jirovecii is a fungus that causes severe pneumonia in immuno-compromised individuals, such as HIV patients. This disease is one of the most common life-threatening invasive fungal infections.
Overcoming technical challenges
To examine how the pathogen could be altering its surface proteins - a mechanism called antigenic variation - in order to evade the human immune system, the team of scientists used a recent sequencing technique, known as PacBio technology. Thanks to this technique, which generates long reads of DNA, the repetitive gene families that encode proteins found on the surface of the fungi have been characterized from a single clinical sample taken from a patient.
"This particular project was particularly demanding," explains first author SIB's Computational Scientist Emanuel Schmid-Siegert, "as we were trying to describe and analyze chromosomal regions that are extremely hard to resolve. They are located in sub-telomeric regions and are very repeat rich."
Recent computational and technical advances in bioinformatics, as well as an important manual curation effort, were necessary to overcome these challenges. "After some initial technical difficulties, we were very proud and happy when we managed to hold assembled regions of major surface glycoproteins in our hands for the first time," concludes Schmid-Siegert.
A quick-change artist strategy
The major surface glycoproteins gene families appeared to be located near the ends of chromosomes, the sub-telomeres. It has been found that this chromosomal localization favours genetic recombination between the members of each gene family, which allows a diversification of these proteins over time.
Pneumocystis jirovecii seems to use a strategy of antigenic variation, which consists of the continuous production of cells that are antigenically different. While this is a widespread strategy in viruses, it is unique among pathogens affecting humans, and could be associated with the particular niche in the lungs of the host.
The study was funded by a grant from the Swiss National Science Foundation to Philippe Hauser (CHUV-UNIL) and Marco Pagni (SIB-UNIL).
Schmid-Siegert E, Richard S, Luraschi A, Mühlethaler K, Pagni M, Hauser PM. Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus Pneumocystis jirovecii. mBio 2017. DOI: 10.1128/mBio.01470-17
Listen to the TWiM podcast 165 on this paper, as of 22'09'' and the focus on E. Schmid-Siegert at 45'25''
From the wet-lab to bioinformatics, a quick bio of Emanuel Schmid-Siegert
1982 Born in Kempten, Germany
2003 -2008 Diploma thesis in biology at the Friedrich-Alexander University of Erlangen (Germany) entitled "Attempts to identify the electrophile signal transduction in Arabidopsis thaliana"
2008 -2013 PhD thesis in molecular plant physiology at the University of Lausanne entitled "A genetic and biochemical investigation of malondialdehyde production and turnover in Arabidopsis thaliana"
2013-2015 Postdoctoral Fellow in SIB's Vital-IT group: trainer in bioinformatics, analysis of various NGS projects
January 2015-today: Computational Scientist in SIB's Vital-IT group. Analysis and interpretation of whole-genome sequencing derived data and plant-related life science projects from cell culture to pathogens
About his work as a computational scientist at SIB, Emanuel says: "I am very fond of the possibility of having a large variety of different research projects with various means of analysis and different organisms. This means in practice, that for each project a different small team is formed from different colleagues in order to obtain the best expertise."