Understanding pneumococcal serotype 1 biology through population genomic analysis.
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.



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.



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.



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.
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK. Chrispin.Chaguza@liverpool.ac.uk.|Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi. Chrispin.Chaguza@liverpool.ac.uk.
Chrispin
0000-0002-2108-1757
C
Chaguza
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.|Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi.
Jennifer E
JE
Cornick
Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
Simon R
SR
Harris
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.|Department of Epidemiology, Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Massachusetts, MA, 02115, USA.
Cheryl P
CP
Andam
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.
Laura
L
Bricio-Moreno
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.
Marie
M
Yang
Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
Feyruz
F
Yalcin
Unité de Biologie, Centre de Recherche Médicale et Sanitaire (CERMES), Niamey, Niger.
Sani
S
Ousmane
National Institute for Communicable Diseases (NICD), Johannesburg, South Africa.
Shanil
S
Govindpersad
Bacterial Diseases Programme, Medical Research Council (MRC), Banjul, The Gambia.|Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
Madikay
M
Senghore
Bacterial Diseases Programme, Medical Research Council (MRC), Banjul, The Gambia.|Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Chinelo
C
Ebruke
National Institute for Communicable Diseases (NICD), Johannesburg, South Africa.
Mignon
M
Du Plessis
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.|Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi.
Anmol M
AM
Kiran
Swiss Tropical and Public Health Institute, Basel, Switzerland.
Gerd
G
Pluschke
Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique.
Betuel
B
Sigauque
Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, GA 30329, USA.
Lesley
L
McGee
Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.|Bill and Melinda Gates Foundation, Seattle, WA, 98109, USA.
Keith P
KP
Klugman
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
Paul
P
Turner
Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.
Jukka
J
Corander
Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
Julian
J
Parkhill
Unité de Biologie, Centre de Recherche Médicale et Sanitaire (CERMES), Niamey, Niger.
Jean-Marc
JM
Collard
Bacterial Diseases Programme, Medical Research Council (MRC), Banjul, The Gambia.|Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.|Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Martin
M
Antonio
National Institute for Communicable Diseases (NICD), Johannesburg, South Africa.|School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Anne
A
von Gottberg
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi.|Division of Infection and Immunity, University College London, London, WC1E 6BT, UK.
Robert S
RS
Heyderman
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.|Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi.
Neil
N
French
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.
Aras
A
Kadioglu
Department of Epidemiology, Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Massachusetts, MA, 02115, USA.
William P
WP
Hanage
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.|Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi.
Dean B
DB
Everett
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK. sdb@sanger.ac.uk.|Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK. sdb@sanger.ac.uk.
Stephen D
SD
Bentley
D000349:Africa; D001208:Asia; D024881:Drug Resistance, Bacterial / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D009305:Nasopharynx / Q000382:microbiology; D010802:Phylogeny; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D011995:Recombination, Genetic; D012641:Selection, Genetic; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D013753:Tetracycline Resistance / Q000235:genetics
Antibiotic resistance; Evolution; Phylogeography; Pneumococcal serotype 1; ST217