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J Clin Microbiol. 2018 Jun 25;56(7). pii: e00228-18. doi: 10.1128/JCM.00228-18. Print 2018 Jul.

Global Distribution of Invasive Serotype 35D Streptococcus pneumoniae Isolates following Introduction of 13-Valent Pneumococcal Conjugate Vaccine.

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Infection Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
Infection Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Vaccines and Immunity Theme, Medical Research Council Unit The Gambia, Banjul, Fajara, The Gambia.
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Institute of Infection & Global Health, University of Liverpool, Liverpool, United Kingdom.
Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa.
Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
Institute of Environmental Science and Research Limited, Kenepuru Science Centre, Porirua, New Zealand.
Hacettepe University Faculty of Medicine, Department of Medical Microbiology, Ankara, Turkey.
Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Department of Microbiology, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, Casablanca, Morocco.
Bacteriology-Virology and Hospital Hygiene Laboratory, University Hospital Centre Ibn Rochd, Casablanca, Morocco.
Department of Pathology and Laboratory Medicine and Department of Paediatrics and Child Health, The Aga Khan University, Karachi, Pakistan.
Faculty of Medicine and Institute of Life Sciences, University of Southampton, Southampton, United Kingdom.
Microbiology and Infection Unit, Warwick Medical School, Warwick, United Kingdom.
London School of Hygiene and Tropical Medicine, London, United Kingdom.
University of Edinburgh, The Queens Medical Research Institute, Edinburgh, United Kingdom.
Emory Global Health Institute, Emory University, Atlanta, Georgia, USA.


A newly recognized pneumococcal serotype, 35D, which differs from the 35B polysaccharide in structure and serology by not binding to factor serum 35a, was recently reported. The genetic basis for this distinctive serology is due to the presence of an inactivating mutation in wciG, which encodes an O-acetyltransferase responsible for O-acetylation of a galactofuranose. Here, we assessed the genomic data of a worldwide pneumococcal collection to identify serotype 35D isolates and understand their geographical distribution, genetic background, and invasiveness potential. Of 21,980 pneumococcal isolates, 444 were originally typed as serotype 35B by PneumoCaT. Analysis of the wciG gene revealed 23 isolates from carriage (n = 4) and disease (n = 19) with partial or complete loss-of-function mutations, including mutations resulting in premature stop codons (n = 22) and an in-frame mutation (n = 1). These were selected for further analysis. The putative 35D isolates were geographically widespread, and 65.2% (15/23) of them was recovered after the introduction of pneumococcal conjugate vaccine 13 (PCV13). Compared with serotype 35B isolates, putative serotype 35D isolates have higher invasive disease potentials based on odds ratios (OR) (11.58; 95% confidence interval[CI], 1.42 to 94.19 versus 0.61; 95% CI, 0.40 to 0.92) and a higher prevalence of macrolide resistance mediated by mefA (26.1% versus 7.6%; P = 0.009). Using the Quellung reaction, 50% (10/20) of viable isolates were identified as serotype 35D, 25% (5/20) as serotype 35B, and 25% (5/20) as a mixture of 35B/35D. The discrepancy between phenotype and genotype requires further investigation. These findings illustrated a global distribution of an invasive serotype, 35D, among young children post-PCV13 introduction and underlined the invasive potential conferred by the loss of O-acetylation in the pneumococcal capsule.


35D; PCV; novel serotype; whole-genome sequencing

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