HIV coinfection is associated with low fitness rpoB variants in rifampicin-resistant Mycobacterium tuberculosis

Loiseau, C.; Brites, D.; Reinhard, M.; Zuercher, K.; Borrell, S.; Ballif, M.; Fenner, L.; Cox, H.; Rutaihwa, L. K.; Wilkinson, R. J.; Yotebieng, M.; Carter, E. J.; Abimiku, A.; Marcy, O.; Gotuzzo, E.; Avihingsanon, A.; Zetola, N.; Doulla, B.; Boettger, E. C.; Egger, M.; Gagneux, S.

doi:10.1101/2020.07.20.208835

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bioRxiv · 10.1101/2020.07.20.208835

HIV coinfection is associated with low fitness rpoB variants in rifampicin-resistant Mycobacterium tuberculosis

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Abstract

We analysed 312 drug-resistant genomes of Mycobacterium tuberculosis (Mtb) collected from HIV coinfected and HIV negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant Mtb strains isolated from HIV coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low fitness rpoB variants can thrive in the context of reduced host immunity.

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Loiseau, C., Brites, D., Reinhard, M., Zuercher, K., Borrell, S., Ballif, M., Fenner, L., Cox, H., Rutaihwa, L. K., Wilkinson, R. J., Yotebieng, M., Carter, E. J., Abimiku, A., Marcy, O., Gotuzzo, E., Avihingsanon, A., Zetola, N., Doulla, B., Boettger, E. C., Egger, M., Gagneux, S.. 2020-07-22. HIV coinfection is associated with low fitness rpoB variants in rifampicin-resistant Mycobacterium tuberculosis. https://doi.org/10.1101/2020.07.20.208835

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