A mosaic tetracycline resistance gene tet(S/M) detected in an MDR pneumococcal CC230 lineage that underwent capsular switching in South Africa

• Type of Material: Article
• Authors: Stephanie W. Lo, Wellcome Sanger Institute; Rebecca A. Gladstone, Wellcome Sanger Institute; Andries J. van Tonder, Wellcome Sanger Institute; Mignon Du Plessis, National Institute for Communicable Diseases; Jennifer E. Cornick, Malawi Liverpool Wellcome Trust Clinic Research Programm; Paulina A. Hawkins, Emory University; Shabir A. Madhi, University of Witwatersrand; Susan A. Nzenze, University of Witwatersrand; Rama Kandasamy, University of Oxford; K. L. Ravikumar, Kempegowda Institute of Medical Sciences; Naima Elmdaghri, Hassan II University of Casablanca; Brenda Kwambana-Adams, University College London; Samantha Cristine Grassi Almeida, Adolfo Lutz Institute; Anna Skoczynska, National Medicines Institute; Ekaterina Egorova, Moscow Research Institute for Epidemiology and Microbiology; Leonid Titov, The Republican Research and Practical Center for Epidemiology and Microbiology; Samir K. Saha, Child Health Research Foundation; Metka Paragi, National Laboratory of Health; Dean B. Everett, University of Edinburgh; Martin Antonio, London School of Hygiene & Tropical Medicine; Keith Klugman, Emory University; Yuan Li, Centers for Disease Control and Prevention; Benjamin J. Metcalf, Centers for Disease Control and Prevention; Bernard Beall, Centers for Disease Control and Prevention; Lesley McGee, Centers for Disease Control and Prevention; Robert Breiman, Emory University; Stephen D. Bentley, Wellcome Sanger Institute; Anne von Gottberg, University of Witwatersrand
• Language: English
• Date: 2020-03-01
• Publisher: Oxford University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/jac/dkz477
• Title of Journal or Parent Work: Journal of Antimicrobial Chemotherapy
• Volume: 75
• Issue: 3
• Start Page: 512
• End Page: 520
• Grant/Funding Information: We would like to acknowledge the Bill & Melinda Gates Foundation (grant code OPP1034556) and the Wellcome Sanger Institute (core Wellcome grants 098051 and 206194) for funding this study, as part of the GPS project.
• Keywords: Science & Technology; Pharmacology & Pharmacy; Serotype 35B; Disease; Identification; Life Sciences & Biomedicine; Infectious Diseases; Microbiology; Vaccination; Spread
• Research Categories: Biology, Parasitology; Biology, Microbiology; Health Sciences, Pharmacology; Health Sciences, Pharmacy

Abstract

Objectives: We reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions. Methods: We whole-genome sequenced 12 254 pneumococcal isolates from 29 countries on an Illumina HiSeq sequencer. Serotype, multilocus ST and antibiotic resistance were inferred from genomes. An SNP tree was built using Gubbins. Temporal spread was reconstructed using a birth-death model. Results: We identified tet(S/M) in 131 pneumococcal isolates and none carried other known tet genes. Tetracycline susceptibility testing results were available for 121 tet(S/M)-positive isolates and all were resistant. A majority (74%) of tet(S/M)-positive isolates were from South Africa and caused invasive diseases among young children (59% HIV positive, where HIV status was available). All but two tet(S/M)-positive isolates belonged to clonal complex (CC) 230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sublineage predicted to exhibit resistance to penicillin, co-trimoxazole, erythromycin and tetracycline. The birth-death model detected an unrecognized outbreak of this sublineage in South Africa between 2000 and 2004 with expected secondary infections (effective reproductive number, R) of ∼2.5. R declined to ∼1.0 in 2005 and <1.0 in 2012. The declining epidemic could be related to improved access to ART in 2004 and introduction of pneumococcal conjugate vaccine (PCV) in 2009. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sublineage. Conclusions: The prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognized outbreak of CC230 in South Africa. Capsular switching in this MDR sublineage highlighted its potential to continue to cause disease in the post-PCV13 era.