Editors' ChoiceInfectious diseases

A molecular warning system for invasive pneumococcus

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Science Translational Medicine  20 Jun 2018:
Vol. 10, Issue 446, eaau0470
DOI: 10.1126/scitranslmed.aau0470

Abstract

A genome-wide association study of Streptococcus pneumoniae identifies and validates bacterial loci associated with invasive infection.

Streptococcus pneumoniae maintains a dichotomous existence as both a virulent pathogen and innocuous member of the upper respiratory microbiome. This split personality has long been appreciated but still remains incompletely understood. Here, Cremers and colleagues address the need for clinically informative prognostic markers of severe infection by evaluating genomic variation in S. pneumoniae from patients with invasive infections.

The authors performed whole-genome sequencing on isolates from 349 patients with pneumococcal bacteremia and interrogated genes, sequence clusters, and allelic variants to identify associations with clinical phenotypes of severe infection. They identified slaA, which encodes human phospholipase A2, as an independent predictor of meningitis. Intriguingly, slaA had previously been reported to enhance virulence and facilitate invasion through the blood-brain barrier in other pathogenic Streptococcus species. They also discovered a cluster of pneumococcal genes colocated on a prophage that were associated with 30-day mortality. Prophages are known to modulate the virulence of many bacterial pathogens, and these findings suggest their detection may have value for clinical risk stratification.

The genomic diversity of S. pneumoniae is reflected in capsular serotype variation and can differ geographically and temporally based on factors such as vaccination coverage. Although the authors validated findings in separate cohorts, further study in additional populations with more divergent pneumococcal serotypes will only add value to this work. Integrating host transcriptional or cytokine profiling with genomic variant analyses could also add an important dimension to these discovery efforts. In addition, future work incorporating coinfecting bacterial and viral pathogens into predictive models of disease severity may illuminate new genotypic associations. Though great potential for future work exists, this study, which elegantly bridges comparative genomics and clinical infectious diseases, sets the stage for developing rapid molecular diagnostics that detect invasive infection.

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