Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
Author:
Lees John A.ORCID, Ferwerda Bart, Kremer Philip H. C., Wheeler Nicole E., Valls Serón Mercedes, Croucher Nicholas J., Gladstone Rebecca A., Bootsma Hester J., Rots Nynke, Wijmega-Monsuur Alienke J., Sanders Elisabeth A. M., Trzciński Krzysztof, Wyllie Anne L., Zwinderman Aeilko H., den Berg Leonard H. van, Rheenen Wouter van, H. Veldink Jan, Harboe Zitta B., Lundbo Lene F., Groot Lisette C. P. G. M. de, Schoor Natasja M. van, Velde Nathalie van der, Ängquist Lars H., Sørensen Thorkild I.A., Nohr Ellen A., Mentzer Alexander J., C. Mills Tara, Knight Julian C., du Plessis Mignon, Nzenze Susan, N. Weiser Jeffrey, Parkhill Julian, Madhi Shabir, Benfield Thomas, von Gottberg Anne, Ende Arie van der, Brouwer Matthijs C., Barrett Jeffrey C., Bentley Stephen D., de Beek Diederik van
Abstract
AbstractStreptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, and identified variants in CCDC33 associated with susceptibility. Pneumococcal variation explained a large amount of invasive potential, but serotype explained only half of this variation. Newly developed methods identified pneumococcal genes involved in invasiveness including pspC and zmpD, and allowed a human-bacteria interaction analysis, finding associations between pneumococcal lineage and STK32C.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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