TY - JOUR
T1 - Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis
AU - Lees, John A.
AU - Ferwerda, Bart
AU - Kremer, Philip H.C.
AU - Wheeler, Nicole E.
AU - Serón, Mercedes Valls
AU - Croucher, Nicholas J.
AU - Gladstone, Rebecca A.
AU - Bootsma, Hester J.
AU - Rots, Nynke Y.
AU - Wijmega-Monsuur, Alienke J.
AU - Sanders, Elisabeth A.M.
AU - Trzciński, Krzysztof
AU - Wyllie, Anne L.
AU - Zwinderman, Aeilko H.
AU - van den Berg, Leonard H.
AU - van Rheenen, Wouter
AU - Veldink, Jan H.
AU - Harboe, Zitta B.
AU - Lundbo, Lene F.
AU - de Groot, Lisette C.P.G.M.
AU - van Schoor, Natasja M.
AU - van der Velde, Nathalie
AU - Ängquist, Lars H.
AU - Sørensen, Thorkild I.A.
AU - Nohr, Ellen A.
AU - Mentzer, Alexander J.
AU - Mills, Tara C.
AU - Knight, Julian C.
AU - du Plessis, Mignon
AU - Nzenze, Susan
AU - Weiser, Jeffrey N.
AU - Parkhill, Julian
AU - Madhi, Shabir
AU - Benfield, Thomas
AU - von Gottberg, Anne
AU - van der Ende, Arie
AU - Brouwer, Matthijs C.
AU - Barrett, Jeffrey C.
AU - Bentley, Stephen D.
AU - van de Beek, Diederik
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Streptococcus 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, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.
AB - Streptococcus 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, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.
UR - http://www.scopus.com/inward/record.url?scp=85065780769&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85065780769&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31092817
U2 - https://doi.org/10.1038/s41467-019-09976-3
DO - https://doi.org/10.1038/s41467-019-09976-3
M3 - Article
C2 - 31092817
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2176
ER -