June 13, 2017 - With an estimated one million cases diagnosed worldwide each year, the human pathogen Cryptococcus neoformans, which can cause life-threatening fungal infections in immunocompromised patients, is an important health concern. In a study published today in Genome Research, scientists identified natural genomic variation in C. neoformans that may influence prevalence and disease severity.
Researchers from the Broad Institute of MIT and Harvard, Duke University Medical Center, and elsewhere sequenced 387 environmental and clinical isolates of C. neoformans predominantly from sub-Saharan Africa, where the disease burden of cryptococcosis is high. Because the pathogen is environmentally acquired and cannot be transmitted human-to-human, any genetic variation leading to changes in virulence must be coincident with other selective pressures.
Using whole-genome sequencing data, the researchers found approximately 1 million variants across samples, and were able to clearly differentiate the three known C. neoformans lineages, VNI, VNII, and VNB. Additionally, VNB could be further subdivided into two previously suggested subgroups, VNBI and VNBII, based on multiple approaches. Notably, the two subgroups showed vastly different frequencies in the environment, with VNBII almost exclusively found in clinical samples. Large scale phenotypic profiling revealed that VNBII clinical isolates are less pigmented, which protects the fungus from environmental stress, and also less resistant to oxidative damage. After characterizing recombination levels in these subgroups, the researchers carried out genome-wide association studies and scans for selective signatures, which identified specific variants associated with clinical isolates including some linked to known virulence factors.
"Our work begins to examine how natural variation contributes to differences in human infection and suggests that some genetic pathways are less important during human infection than for growth in the environment," said corresponding author and Senior Group Leader, Fungal Genomics at the Broad Institute, Christina Cuomo said.
Researchers from the Broad Institute, Duke University Medical Center, University of Pennsylvania, and the Centers for Disease Control and Prevention contributed to this work. The study was funded by the National Institute of Allergy and Infectious Diseases and the U.S. Public Health Service.
The authors are available for more information by contacting: Lee McGuire, Broad Institute of MIT and Harvard, firstname.lastname@example.org.
Interested reporters may obtain copies of the manuscript via email from Dana Macciola, Administrative Assistant, Genome Research, email@example.com; +1-516-422-4012.
About the article:
The manuscript will be published online ahead of print on 13 June 2017. Its full citation is as follows: Desjardins CA, Giamberardino C, Sykes SM, Yu C, Tenor JL, Chen Y, Yang T, Jones AM, Sun S, Haverkamp MR, Heitman J, Litvintseva AP, Perfect JR, Cuomo CA. 2017. Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans. Genome Res doi: 10.1101/gr.218727.116
About Genome Research:
Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.
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Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. The Press is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit our website at http://cshlpress.
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