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Open Access Highly Accessed Research article

Comparative phylogenomics of Streptococcus pneumoniae isolated from invasive disease and nasopharyngeal carriage from West Africans

Eric S Donkor15, Richard A Stabler1, Jason Hinds3, Richard A Adegbola4, Martin Antonio2 and Brendan W Wren1*

Author Affiliations

1 Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK

2 Vaccinology Theme, Medical Research Council Unit, The Gambia

3 Bacterial Microarray Group, St. George’s University of London, London, SW17 0RE, UK

4 GlaxoSmithKline Vaccines, Wavre, Belgium

5 Department of Microbiology, University of Ghana Medical School, Accra, Ghana

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BMC Genomics 2012, 13:569  doi:10.1186/1471-2164-13-569

Published: 29 October 2012

Abstract

Background

We applied comparative phylogenomics (whole genome comparisons of microbes using DNA microarrays combined with Bayesian-based phylogenies) to investigate S. pneumoniae isolates from West Africa, with the aim of providing insights into the pathogenicity and other features related to the biology of the organism. The strains investigated comprised a well defined collection of 58 invasive and carriage isolates that were sequenced typed and included eight different S. pneumoniae serotypes (1, 3, 5, 6A, 11, 14, 19 F and 23 F) of varying invasive disease potential.

Results

The core genome of the isolates was estimated to be 38% and was mainly represented by gene functional categories associated with housekeeping functions. Comparison of the gene content of invasive and carriage isolates identified at least eleven potential genes that may be important in virulence including surface proteins, transport proteins, transcription factors and hypothetical proteins. Thirteen accessory regions (ARs) were also identified and did not show any loci association with the eleven virulence genes. Intraclonal diversity (isolates of the same serotype and MLST but expressing different patterns of ARs) was observed among some clones including ST 1233 (serotype 5), ST 3404 (serotype 5) and ST 3321 (serotype 14). A constructed phylogenetic tree of the isolates showed a high level of heterogeneity consistent with the frequent S. pneumoniae recombination. Despite this, a homogeneous clustering of all the serotype 1 strains was observed.

Conclusions

Comparative phylogenomics of invasive and carriage S. pneumoniae isolates identified a number of putative virulence determinants that may be important in the progression of S. pneumoniae from the carriage phase to invasive disease. Virulence determinants that contribute to S. pneumoniae pathogenicity are likely to be distributed randomly throughout its genome rather than being clustered in dedicated loci or islands. Compared to other S. pneumoniae serotypes, serotype 1 appears most genetically uniform.