A novel mosaic tetracycline resistance gene tet(S/M) detected in a multidrug-resistant pneumococcal CC230 lineage that underwent capsular switching in South Africa

Lo, S. W.; Gladstone, R. A.; van Tonder, A. J.; du Plessis, M.; Cornick, J. E.; Hawkins, P. A.; Madhi, S. A.; Nzenze, S. A.; Kandasamy, R.; Ravikumar, K.; Elmdaghri, N.; Kwambana-Adams, B.; Almeida, S. C. G.; Skoczynska, A.; Egorova, E.; Titov, L.; Saha, S. K.; Paragi, M.; Everett, D. B.; Antonio, M.; Klugman, K. P.; Li, Y.; Metcalf, B. J.; Beall, B.; McGee, L.; Breiman, R. F.; Bentley, S. D.; von Gottberg, A.

doi:10.1101/718460

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bioRxiv · 10.1101/718460

A novel mosaic tetracycline resistance gene tet(S/M) detected in a multidrug-resistant pneumococcal CC230 lineage that underwent capsular switching in South Africa

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Abstract

SynopsisO_ST_ABSObjectiveC_ST_ABSWe reported a novel tetracycline-resistant gene in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions.\n\nMethodsWe whole genome sequenced 12,254 pneumococcal isolates from twenty-nine countries on an Illumina HiSeq Sequencer. Serotypes, sequence types and antibiotic resistance were inferred from genomes. Phylogeny was built based on single-nucleotide variants. Temporal changes of spread were reconstructed using a birth-death model.\n\nResultsWe identified tet(S/M) in 131 pneumococcal isolates, 97 (74%) caused invasive pneumococcal diseases among young children (59% HIV-positive, where HIV status was available) in South Africa. A majority of tet(S/M)-positive isolates (129/131) belong to clonal complex (CC)230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sub-lineage that exhibited multidrug-resistance. Using the genomic data and a birth-death model, we detected an unrecognised outbreak of this sub-lineage in South Africa between 2000 and 2004 with an expected secondary infections (R) of ~2.5. R declined to ~1.0 in 2005 and <1.0 in 2012. The declining epidemic coincided and could be related to the nationwide implementation of anti-retroviral treatment (ART) for HIV-infected individuals in 2004 and PCVs in late 2000s. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sub-lineage.\n\nConclusionsThe prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognised outbreak of CC230 in South Africa prior to ART and PCVs. However, capsular switching in this multidrug-resistant sub-lineage highlighted its potential to continue to cause disease in the post-PCV13 era.

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Lo, S. W., Gladstone, R. A., van Tonder, A. J., du Plessis, M., Cornick, J. E., Hawkins, P. A., Madhi, S. A., Nzenze, S. A., Kandasamy, R., Ravikumar, K., Elmdaghri, N., Kwambana-Adams, B., Almeida, S. C. G., Skoczynska, A., Egorova, E., Titov, L., Saha, S. K., Paragi, M., Everett, D. B., Antonio, M., Klugman, K. P., Li, Y., Metcalf, B. J., Beall, B., McGee, L., Breiman, R. F., Bentley, S. D., von Gottberg, A.. 2019-07-30. A novel mosaic tetracycline resistance gene tet(S/M) detected in a multidrug-resistant pneumococcal CC230 lineage that underwent capsular switching in South Africa. https://doi.org/10.1101/718460

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