Genome Analysis of a Highly Virulent Serotype 1 Strain of Streptococcus pneumoniae from West Africa

Tiffany M Williams,Daniel M Musher,Chinelo Ebruke,Martin Antonio,Mark J Pallen,Nicholas J Loman,George M Weinstock,Richard A Adegbola,Stefan Bereswill

doi:10.1371/journal.pone.0026742

Abstract

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia, estimated to cause 2 million deaths annually. The majority of pneumococcal mortality occurs in developing countries, with serotype 1 a leading cause in these areas. To begin to better understand the larger impact that serotype 1 strains have in developing countries, we characterized virulence and genetic content of PNI0373, a serotype 1 strain from a diseased patient in The Gambia. PNI0373 and another African serotype 1 strain showed high virulence in a mouse intraperitoneal challenge model, with 20% survival at a dose of 1 cfu. The PNI0373 genome sequence was similar in structure to other pneumococci, with the exception of a 100 kb inversion. PNI0373 showed only15 lineage specific CDS when compared to the pan-genome of pneumococcus. However analysis of non-core orthologs of pneumococcal genomes, showed serotype 1 strains to be closely related. Three regions were found to be serotype 1 associated and likely products of horizontal gene transfer. A detailed inventory of known virulence factors showed that some functions associated with colonization were absent, consistent with the observation that carriage of this highly virulent serotype is unusual. The African serotype 1 strains thus appear to be closely related to each other and different from other pneumococci despite similar genetic content.

Highlights

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia, collectively termed invasive pneumococcal disease (IPD) [1,2]
It is estimated that S. pneumoniae is responsible for 2 million deaths annually, with 0.7–1 million of these occurring in children, five years of age [3,4,5]
The case fatality rate for IPD ranges from 11% for pneumonia among adults within industrialized nations to .50% for meningitis within children,5 years of age in sub-Saharan Africa, the majority of pneumococcal mortality occurring in developing countries [6,7,8]

Summary

Introduction

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia, collectively termed invasive pneumococcal disease (IPD) [1,2]. The case fatality rate for IPD ranges from 11% for pneumonia among adults within industrialized nations to .50% for meningitis within children ,5 years of age in sub-Saharan Africa, the majority of pneumococcal mortality occurring in developing countries [6,7,8]. In many of high pneumococcal burden countries within Africa, Asia and Latin America, serotype 1 consistently ranks among the most prevalent IPD-causing serotypes in children and adults [9,10,11,12,13]. Within the African meningitis belt, characterized by its high incidence of meningitis and associated mortality, almost 60% of pneumococcal meningitis is attributable to serotype 1 strains [21]. No evidence of protection against serotype 1 was apparent in Gambian and South African trials evaluating an expanded pneumococcal glycoconjugate vaccine, which included the serotype 1 glycoprotein, the total serotype 1 cases were small and statistical power was insufficient to draw conclusions [22,23]

Methods

Results

Conclusion