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Understanding pneumococcal serotype 1 biology through population genomic analysis

Chrispin Chaguza 1, 2, * Jennifer Cornick 1, 2 Simon Harris 3 Cheryl Andam 1, 4 Laura Bricio-Moreno 1 Marie Yang 1 Feyruz Yalcin 3 Sani Ousmane 5 Shanil Govindpersad 6 Madikay Senghore 7, 8 Chinelo Ebruke 7, 9 Mignon Du Plessis 6 Anmol Kiran 1, 2 Gerd Pluschke 10 Betuel Sigauque 11 Lesley Mcgee 12 Keith Klugman 13, 14 Paul Turner 15, 16 Jukka Corander 17 Julian Parkhill 3 Jean-Marc Collard 5 Martin Antonio 7, 8, 9 Anne von Gottberg 6, 18 Robert Heyderman 2, 19 Neil French 1, 2 Aras Kadioglu 1 William Hanage 4 Dean Everett 1, 2 Stephen Bentley 1, 3, * The Page Consortium
* Corresponding author
1 University of Liverpool
2 MLW - Malawi Liverpool Wellcome Trust Clinical Research Programme
LSTM - Liverpool School of Tropical Medicine, University of Liverpool, Wellcome Trust, University of Malawi
3 The Wellcome Trust Sanger Institute [Cambridge]
4 Harvard T.H. Chan School of Public Health
5 CERMES - Centre de Recherche Médicale et Sanitaire (Niamey, Niger)
6 NICD - National Institute for Communicable Diseases [Johannesburg]
7 MRC - Medical Research Council Unit The Gambia
8 University of Warwick [Coventry]
9 LSHTM - London School of Hygiene and Tropical Medicine
10 Swiss Tropical and Public Health Institute [Basel]
11 CISM - Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique]
12 CDC - Centers for Disease Control and Prevention [Atlanta]
13 Emory University [Atlanta, GA]
14 Bill & Melinda Gates Foundation [Seattle]
15 AHC - Angkor Hospital for Children
16 University of Oxford [Oxford]
17 University of Helsinki
18 WITS - University of the Witwatersrand [Johannesburg]
19 UCL - University College of London [London]
Abstract : Background Pneumococcus kills over one million children annually and over 90 % of these deaths occur in low-income countries especially in Sub-Saharan Africa (SSA) where HIV exacerbates the disease burden. In SSA, serotype 1 pneumococci particularly the endemic ST217 clone, causes majority of the pneumococcal disease burden. To understand the evolution of the virulent ST217 clone, we analysed ST217 whole genomes from isolates sampled from African and Asian countries. Methods We analysed 226 whole genome sequences from the ST217 lineage sampled from 9 African and 4 Asian countries. We constructed a whole genome alignment and used it for phylogenetic and coalescent analyses. We also screened the genomes to determine presence of antibiotic resistance conferring genes. Results Population structure analysis grouped the ST217 isolates into five sequence clusters (SCs), which were highly associated with different geographical regions and showed limited intracontinental and intercontinental spread. The SCs showed lower than expected genomic sequence, which suggested strong purifying selection and small population sizes caused by bottlenecks. Recombination rates varied between the SCs but were lower than in other successful clones such as PMEN1. African isolates showed higher prevalence of antibiotic resistance genes than Asian isolates. Interestingly, certain West African isolates harbored a defective chloramphenicol and tetracycline resistance-conferring element (Tn5253) with a deletion in the loci encoding the chloramphenicol resistance gene (catpC194), which caused lower chloramphenicol than tetracycline resistance. Furthermore, certain genes that promote colonisation were absent in the isolates, which may contribute to serotype 1’s rarity in carriage and consequently its lower recombination rates. Conclusions The high phylogeographic diversity of the ST217 clone shows that this clone has been in circulation globally for a long time, which allowed its diversification and adaptation in different geographical regions. Such geographic adaptation reflects local variations in selection pressures in different locales. Further studies will be required to fully understand the biological mechanisms which makes the ST217 clone highly invasive but unable to successfully colonise the human nasopharynx for long durations which results in lower recombination rates.
Keywords : Antibiotic resistance Evolution Phylogeography Pneumococcal serotype 1 ST217
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Chrispin Chaguza, Jennifer Cornick, Simon Harris, Cheryl Andam, Laura Bricio-Moreno, et al.. Understanding pneumococcal serotype 1 biology through population genomic analysis. BMC Infectious Diseases, BioMed Central, 2016, 16 (1), pp.649. ⟨10.1186/s12879-016-1987-z⟩. ⟨pasteur-03238485⟩

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