Borderline rpoB mutations transmit at the same rate as common rpoB mutations in a tuberculosis cohort in Bangladesh

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Lempens, P, Van Deun, A, Aung, KJM, Hossain, MA, Behruznia, M ORCID: https://orcid.org/0000-0002-3302-7272, Decroo, T, Rigouts, L, de Jong, BC and Meehan, CJ ORCID: https://orcid.org/0000-0003-0724-8343, 2023. Borderline rpoB mutations transmit at the same rate as common rpoB mutations in a tuberculosis cohort in Bangladesh. Microbial Genomics, 9 (9): 001109. ISSN 2057-5858

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Official URL: https://doi.org/10.1099/mgen.0.001109

Abstract

The spread of multidrug-resistant tuberculosis (MDR-TB) is a growing problem in many countries worldwide. Resistance to one of the primary first-line drugs, rifampicin, is caused by mutations in the Mycobacterium tuberculosis rpoB gene. So-called borderline rpoB mutations confer low-level resistance, in contrast to more common rpoB mutations which confer high-level resistance. While some borderline mutations show lower fitness in vitro than common mutations, their in vivo fitness is currently unknown. We used a dataset of 394 whole genome sequenced MDR-TB isolates from Bangladesh, representing around 44 % of notified MDR-TB cases over 6 years, to look at differences in transmission clustering between isolates with borderline rpoB mutations and those with common rpoB mutations. We found a relatively low percentage of transmission clustering in the dataset (34.8 %) but no difference in clustering between different types of rpoB mutations. Compensatory mutations in rpoA, rpoB, and rpoC were associated with higher levels of transmission clustering as were lineages two, three, and four relative to lineage one. Young people as well as patients with high sputum smear positive TB were more likely to be in a transmission cluster. Our findings show that although borderline rpoB mutations have lower in vitro growth potential this does not translate into lower transmission potential or in vivo fitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities.

Item Type:	Journal article
Publication Title:	Microbial Genomics
Creators:	Lempens, P., Van Deun, A., Aung, K.J.M., Hossain, M.A., Behruznia, M., Decroo, T., Rigouts, L., de Jong, B.C. and Meehan, C.J.
Publisher:	Microbiology Society
Date:	26 September 2023
Volume:	9
Number:	9
ISSN:	2057-5858
Identifiers:	Number Type 10.1099/mgen.0.001109 DOI 1822031 Other
Rights:	This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	19 Oct 2023 08:28
Last Modified:	19 Oct 2023 08:28
URI:	https://irep.ntu.ac.uk/id/eprint/50012