Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

• DOI: 10.1038/s41467-019-09976-3
• Publication Date: 2019-05-15T10:03:46Z
• Authors: John A. Lees; Bart Ferwerda; Philip H. C. Kremer; Nicole E. Wheeler; Mercedes Valls Serón; Nicholas J. Croucher; Rebecca A. Gladstone; Hester J. Bootsma; Nynke Y. Rots; Alienke J. Wijmeg...; Elisabeth A. M. S...; Krzysztof Trzciński; Anne L. Wyllie; Aeilko H. Zwinderman; Leonard H. van de...; Wouter van Rheenen; Jan H. Veldink; Zitta B. Harboe; Lene F. Lundbo; Lisette C. P. G. ...; Natasja M. van Sc...; Nathalie van der ...; Lars H. Ängquist; Thorkild I. A. Sø...; Ellen A. Nohr; Alexander J. Mentzer; Tara C. Mills; Julian C. Knight; Mignon du Plessis; Susan Nzenze; Jeffrey N. Weiser; Julian Parkhill; Shabir Madhi; Thomas Benfield; Anne von Gottberg; Arie van der Ende; Matthijs C. Brouwer; Jeffrey C. Barrett; Stephen D. Bentley; Diederik van de Beek
• Keywords: Human pathogen; Bacteremia; Pneumococcal infections

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 pathogen known to play role in pneumococcal disease, though what extent unknown. In genome-wide association study human we show that explains almost half susceptibility meningitis one-third severity, identifying variants CCDC33 associated with susceptibility. Pneumococcal genetic large amount potential (70%), has no effect on severity. Serotype alone insufficient explain invasiveness, suggesting other factors are involved progression disease. We identify genes invasiveness including pspC zmpD, perform human-bacteria interaction analysis. These candidates for the development more broadly-acting vaccines.