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

Pauline Lempens, Armand Van Deun, Kya J M Aung, Mohammad A Hossain, Mahboobeh Behruznia, Tom Decroo, Leen Rigouts, Bouke C de Jong, Conor J Meehan

Research output: Contribution to journalA1: Web of Science-articlepeer-review

31 Downloads (Pure)

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.

Original languageEnglish
Article numbere001109
JournalMicrobial Genomics
Volume9
Issue number9
Number of pages9
ISSN2057-5858
DOIs
Publication statusPublished - 2023

Keywords

  • Humans
  • Bangladesh/epidemiology
  • Mutation
  • Rifampin/pharmacology
  • Tuberculosis, Multidrug-Resistant
  • Mycobacterium tuberculosis/genetics
  • Bacterial Proteins/genetics

Fingerprint

Dive into the research topics of 'Borderline rpoB mutations transmit at the same rate as common rpoB mutations in a tuberculosis cohort in Bangladesh'. Together they form a unique fingerprint.

Cite this