A mosaic tetracycline resistance gene tet(S/M) detected in an MDR pneumococcal CC230 lineage that underwent capsular switching in South Africa
Authors: Lo Stephanie W , Gladstone Rebecca A , van Tonder Andries J , Du Plessis Mignon , Cornick Jennifer E , Hawkins Paulina A , Madhi Shabir A , Nzenze Susan A , Kandasamy Rama , Ravikumar K L , Elmdaghri Naima , Kwambana-Adams Brenda , Almeida Samanta Cristine Grassi , Skoczynska Anna , Egorova Ekaterina , Titov Leonid , Saha Samir K , Paragi Metka , Everett Dean B , Antonio Martin , Klugman Keith P , Li Yuan , Metcalf Benjamin J , Beall Bernard , McGee Lesley , Breiman Robert F , Bentley Stephen D , von Gottberg Anne ,   Global Pneumococcal Sequencing Consortium, Brooks Abdullah W , Corso Alejandra , Davydov Alexander , Maguire Alison , Pollard Andrew J , Kiran Anmol , Skoczynska Anna , Moiane Benild , Sigauque Betuel , Aanensen David , Lehmann Deborah , Faccone Diego , Foster-Nyarko Ebenezer , Bojang Ebrima , Voropaeva Elena , Sampane-Donkor Eric , Sadowy Ewa , Nagaraj Geetha , Bigogo Godfrey , Mucavele Helio , Belabbès Houria , Diawara Idrissa , Moïsi Jennifer , Verani Jennifer , Keenan Jeremy , Nair Thulasee Bhai Jyothish N , Ndlangisa Kedibone M , Zerouali Khalid , De Gouveia Linda , Alaerts Maaike , de Cunto Brandileone Maria-Cristina , Ip Margaret , Hasanuzzaman Md , Paragi Metka , Ali Mushal , Croucher Nicholas , Wolter Nicole , Givon-Lavi Noga , Eser Özgen Köseoglu , Ho Pak Leung , Akpaka Patrick E , Turner Paul , Gagetti Paula , Tientcheu Peggy-Estelle , Carter Philip E , Law Pierra , Benisty Rachel , Mostowy Rafal , Ford Rebecca , Henderson Rebecca , Malaker Roly , Dagan Ron , Shakoor Sadia , Doiphode Sanjay , Doiphode Sanjay , Sekaran Shamala Devi , Srifuengfung Somporn , Sekaran Shamala Devi , Srifuengfung Somporn , Obaro Stephen , Clarke Stuart C , Kastrin Tamara , Ochoa Theresa J , Hryniewicz Waleria , Balaji Veeraraghavan , Urban Yulia 
Published: November 2019

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 &lt;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.