Dataset Information

Genotyped_bacterial_meningitis

ABSTRACT: This study includes 1146 samples of host genotyping data (genotyped) from Illumina Omni arrays. Samples were collected from adults (>16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015. Metadata includes patient outcome, species of bacteria, and for 467 samples a link to an ENA run with the associated bacterial genome (S. pneumoniae only).

PROVIDER: EGAD00010002328 | EGA |

REPOSITORIES: EGA

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Publications

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

Lees John A JA Ferwerda Bart B Kremer Philip H C PHC Wheeler Nicole E NE Serón Mercedes Valls MV Croucher Nicholas J NJ Gladstone Rebecca A RA Bootsma Hester J HJ Rots Nynke Y NY Wijmega-Monsuur Alienke J AJ Sanders Elisabeth A M EAM Trzciński Krzysztof K Wyllie Anne L AL Zwinderman Aeilko H AH van den Berg Leonard H LH van Rheenen Wouter W Veldink Jan H JH Harboe Zitta B ZB Lundbo Lene F LF de Groot Lisette C P G M LCPGM van Schoor Natasja M NM van der Velde Nathalie N Ängquist Lars H LH Sørensen Thorkild I A TIA Nohr Ellen A EA Mentzer Alexander J AJ Mills Tara C TC Knight Julian C JC du Plessis Mignon M Nzenze Susan S Weiser Jeffrey N JN Parkhill Julian J Madhi Shabir S Benfield Thomas T von Gottberg Anne A van der Ende Arie A Brouwer Matthijs C MC Barrett Jeffrey C JC Bentley Stephen D SD van de Beek Diederik D

Nature communications 20190515 1

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, ide ...[more]

PMID: 31092817

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Project description:Background Mortality from bacterial meningitis, predominately caused by Streptococcus pneumoniae, exceeds 50% in low and middle income countries in sub-Saharan Africa with high HIV prevalence. Underlying causes of high mortality are poorly understood. We examined the host and pathogen proteome in adults with proven pneumococcal meningitis (PM), testing if differentially expressed proteins in CSF were implicated in outcome. Materials/methods CSF proteomes were analysed by quantitative Mass-Spectrometry. Spectra were identified using the Swissprot human and TIGR4 pneumococcal protein libraries. Proteins were quantitated and analysed against clinical outcome. Unique proteins in PM were identified against published normal CSF proteome. Random-Forest models were used to test for protein signatures discriminating outcome. Proteins of interest were tested for their effects on growth and opsonophagocytic killing of S. pneumoniae. Results CSF proteomes were available for 57 Adults with PM (median age 32 years, 60% male, 70% HIV-1 co-infected, mortality 63%). 360 individual human and 23 pneumococcal proteins were identified. Of the human protein hits, 30% were not expressed in normal CSF, and these were strongly associated with inflammation and primarily related to neutrophil activity. No human protein signature predicted outcome. However, expression of the essential S. pneumoniae protein Elongation Factor Tu (EF-Tu) was significantly increased in CSF of non-survivors (False Discovery Rate (q) <0.001). Expression of EF-Tu was negatively co-correlated against expression of Neutrophil defensin (r 0.4 p p<0.002), but not against complement proteins C3 or Factor H. In vitro, addition of EF-Tu protein impaired S. pneumoniae neutrophil killing when osponised with CSF. Conclusions Excessive CSF levels of S. pneumoniae EF-Tu protein was associated with reduced survival in human meningitis. Preliminary studies show EF-Tu inhibits neutrophil mediated killing of S. pneumoniae in CSF. Further functional studies are required to better understand the mechanistic role of EF-Tu during PM.

Dataset Information

Genotyped_bacterial_meningitis

Publications

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

Similar Datasets

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