Abstract
ObjectivesWe reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions.MethodsWe 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.ResultsWe 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.ConclusionsThe 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.
Highlights
Streptococcus pneumoniae is a major bacterial cause of disease in young children
In South Africa, tet(S/M) was found in 3.5% (103/2920) of the invasive isolates that were submitted to the Global Pneumococcal Sequencing (GPS) project from 2005 to 2014 and 1.2% (20/1701) of the carriage isolates that were collected in Agincourt and Soweto between 2009 and 2013
The tet(S/M) in this study showed 100% nucleotide identity, except for one isolate (GPS_ZA_1982) from South Africa, which varied from the others (G1769A) and resulted in the substitution R590Q
Summary
Streptococcus pneumoniae is a major bacterial cause of disease in young children. Despite the success of pneumococcal conjugate vaccines (PCVs), invasive pneumococcal disease (IPD) remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes, a phenomenon known as serotype replacement.[1]. Resistance to tetracycline has been frequently observed in S. pneumoniae.[6] The genetic basis was shown to be tet(M), and less commonly tet(O), which encode for a ribosomal protection protein that prevents tetracycline binding to the bacterial 30S ribosome subunit.[6,7] Eleven other classes of ribosomal protection proteins such as tet(S) and 12 mosaic structures of tet genes such as tet(S/M) have not been found previously in pneumococci (http://faculty.washington.edu/marilynr/). The mosaic tet(S/M) has been observed on a Tn916 element in Streptococcus intermedius[11] and an IS1216 composite in Streptococcus bovis.[12] Using a dataset of 12 254 pneumococcal genomes from the Global Pneumococcal Sequencing (GPS) project (https://www.pneumogen.net/gps/), we identified a novel genetic basis for tetracycline resistance in S. pneumoniae, tet(S/M), and characterized its genetic background in relation to nationwide clinical interventions
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
