Editors' ChoiceInfectious Disease

Raff-ining our understanding of pneumococcal invasion

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Science Translational Medicine  06 Feb 2019:
Vol. 11, Issue 478, eaaw5322
DOI: 10.1126/scitranslmed.aaw5322

Abstract

Differential raffinose metabolism influences Streptococcus pneumoniae tissue tropism and disease phenotype.

Streptococcus pneumoniae is one of the most common causes of pneumonia, sepsis, and central nervous system (CNS) infections. Paradoxically, in most cases, the pneumococcus is found as an incidental commensal in the human upper respiratory tract and only in certain settings does it invade into the lungs, bloodstream, or CNS. The factors governing S. pneumoniae pathogenicity and site of tissue invasion have remained unclear. Here, Minhas and colleagues identified critical factors governing tissue-specific tropism and invasion by coupling comparative genomics with functional assays both in vitro and in vivo in a murine infection model.

The authors first analyzed matched pneumococcal isolates derived from the same serotypes with distinct tropism for ear/CNS or lung/bloodstream invasion. Following sequencing and genome assembly, they screened for single nucleotide polymorphisms. Although several were identified, only those in genes governing the uptake and use of raffinose, a potentially strategic bacterial energy source, differed between isolates. Phenotypic assays confirmed differential growth in raffinose-supplemented media. Subsequent infection assays demonstrated equivalent nasopharyngeal colonization but different invasiveness into the lungs versus the CNS. Lastly, exchange mutagenesis experiments demonstrated that the identified raffinose metabolism alleles were necessary and sufficient to determine site of tissue invasion.

Minhas and colleagues make an important contribution by identifying a novel pathway governing the disease phenotype of S. pneumoniae. With 98 serotypes and over 12,000 clonal lineages, confirming the generalizability of these findings across other serotypes, and in humans, will be important next steps. Whether raffinose utilization affects tissue tropism and disease phenotype for other contextually pathogenic bacteria is a key outstanding question. In addition, understanding the influence of the airway microbiome on raffinose bioavailability, and thus pneumococcal invasiveness, will be a key aim for future studies.

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