Population genomics of disease-causing streptococcus pneumonia in Singapore

Abstract

The World Health Organization (WHO) reports that approximately 500,000 deaths in children aged 0-59 months occur due to pneumococcal infections and that, in the developing world, pneumococcal pneumonia is the leading infectious cause of adult mortality. Pneumococcal diseases mainly affect the vulnerable populations: children under the age of five years (otitis media is very common), elderly and immunocompromised (most commonly pneumonia). Two thousand and one hundred fifty six pneumococcal isolates causing invasive and non-invasive diseases between 1997 and 2013 were collected from four hospitals in Singapore. The isolates were characterized using whole genome sequencing (WGS). Out of 67 serotypes found throughout the study period, the most common serotypes were 19F, 19A, 14, 23F and the recently reported serotype 6E. Estimated serotype coverage by the current pneumococcal vaccines (PCV-7, -10, -13 and PPV23) ranged from 50% to 74%. Further interrogation of the whole genome data classified isolates into 24 major clusters based on their core orthologous genes. As expected, the same serotypes and similar sequence types (STs) clustered together. Among the 512 STs found, the majority of novel STs were found in isolates from adults. Genetically diverse, rrgC genes (encoding pilin components) were more likely to be found in non-invasive disease-causing isolates while other genes previously associated with pneumococcal virulence, pspA, pspC and ply, were just as likely to be found among non-invasive and invasive disease causing isolates. This first large-scale pneumococcal study from Singapore includes analysis of WGS and clinical data from pneumococcal strains collected over the past 15 years. High genetic diversity identified among these strains may reflect the cosmopolitan nature of Singapore’s increasingly international population and might be a focus for the emergence of novel pneumococcal clones in the era of modern conjugate and protein-based pneumococcal vaccines.

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ORCID for Stuart Clarke: orcid.org/0000-0002-7009-1548

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