Understanding pneumococcal serotype 1 biology through population genomic analysis

• Type of Material: Article
• Authors: Chrispin Chaguza, University of Liverpool; Jennifer E. Cornick, University of Liverpool; Simon R. Harris, Wellcome Trust Sanger Institute; Cheryl P. Andam, University of Liverpool; Laura Bricio-Moreno, University of Liverpool; Marie Yang, University of Liverpool; Feyruz Yalcin, Wellcome Trust Sanger Institute; Sani Ousmane, Centre de Recherche Médicale et Sanitaire; Shanil Govindpersad, National Institute for Communicable Diseases; Madikay Senghore, University of Warwick; Chinelo Ebruke, Medical Research Council; Mignon Du Plessis, National Institute for Communicable Diseases; Anmol M. Kiran, University of Liverpool; Gerd Pluschke, Swiss Tropical and Public Health Institute; Betuel Sigauque, Centro de Investigação em Saúde da Manhiça; Lesley McGee, Centers for Disease Control and Prevention; Keith Klugman, Emory University; Paul Turner, Angkor Hospital for Children; Jukka Corander, Unité de Biologie, Centre de Recherche Médicale et Sanitaire; Julian Parkhill, Wellcome Trust Genome Campus; Jean-Marc Collard, Unité de Biologie, Centre de Recherche Médicale et Sanitaire; Martin Antonio, Medical Research Council; Anne von Gottberg, National Institute for Communicable Diseases; Robert S. Heyderman, Queen Elizabeth Cent Hosp; Neil French, University of Liverpool; Aras Kadioglu, University of Liverpool; William P. Hanage, Harvard University; Dean B. Everett, University of Liverpool; Stephen D. Bentley, University of Liverpool
• Language: English
• Date: 2016-11-08
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12879-016-1987-z
• Title of Journal or Parent Work: BMC Infectious Diseases
• ISSN: 1471-2334
• Volume: 16
• Issue: 1
• Start Page: 649
• End Page: 649
• Grant/Funding Information: This work was supported by funds from the Bill and Melinda Gates Foundation (BMGF) (grant number: OPP1023440 awarded to DBE and The Wellcome Trust Major Overseas programme core award (Award number: 084679/Z/08/Z).
• Keywords: ST217; Pneumococcal serotype 1; RECOMBINATION; Science & Technology; SEROLOGICAL CHARACTERIZATION; Infectious Diseases; Antibiotic resistance; DISCOVERY; Evolution; VIRULENCE FACTORS; CONJUGATE VACCINE; MENINGITIS; STREPTOCOCCUS-PNEUMONIAE; GENERATION; DNA-SEQUENCES; INVASIVE-DISEASE; Life Sciences & Biomedicine; Phylogeography
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Immunology

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 (cat pC194), 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.