BorderlinerpoBmutations transmit at the same rate as commonrpoBmutations in a tuberculosis cohort in Bangladesh

Abstract

AbstractThe 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 theMycobacterium tuberculosis rpoBgene. While some of these infrequent mutations show lower fitnessin vitrothan more common mutations, theirin vivofitness 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 borderlinerpoBmutations and those with commonrpoBmutations. We found a relatively low percentage of transmission clustering in the dataset (34.8%) but no difference in clustering between different types ofrpoBmutations. Compensatory mutations inrpoA, rpoB, andrpoCwere associated with higher levels of transmission clustering as were lineages 2, 3, and 4 relative to lineage 1. 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 borderlinerpoBmutations have lowerin vitrogrowth potential this does not translate into lower transmission potential orin vivofitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities.Data summaryWGS reads are available in the European Nucleotide Archive (PRJEB39569). In addition, WGS reads, as well as pDST and clinical data, are included in the ReSeqTB data platform and are accessible on registration athttps://platform.reseqtb.org/. Custom scripts for clustering are available athttps://github.com/conmeehan/pathophy.