HIV Coinfection Is Associated with Low-Fitness rpoB Variants in Rifampicin-Resistant Mycobacterium tuberculosis.

Chloé Loiseau,Anchalee Avihingsanon,Lukas Fenner,Marie Ballif,Erik C Böttger,Daniela Brites,Helen Cox,Kathrin Zürcher,Olivier Marcy,Eduardo Gotuzzo,Liliana K Rutaihwa,Miriam Reinhard,Matthias Egger,Robert J Wilkinson,Basra Doulla,Marcel Yotebieng,Alash’le Abimiku ,Sònia Borrell ,Nicola M Zetola ,E Jane Carter ,Sébastien Gagneux

doi:10.1128/aac.00782-20

Abstract

We analyzed 312 drug-resistant genomes of Mycobacterium tuberculosis isolates collected from HIV-coinfected and HIV-negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant M. tuberculosis 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.

Highlights

Tuberculosis (TB), caused by members of the Mycobacterium tuberculosis complex, is a leading cause of death worldwide, killing more people than any other infectious disease
The propensity of drug-resistant M. tuberculosis strains to spread is influenced by the fitness cost associated with drug resistance determinants [6]
Bacterial strains that have acquired drug resistance-conferring mutations may be less transmissible than their susceptible counterparts, this fitness cost can be ameliorated by compensatory mutations [7,8,9,10]

Summary

EPIDEMIOLOGY AND SURVEILLANCE crossm

Chloé Loiseau,a,b Daniela Brites,a,b Miriam Reinhard,a,b Kathrin Zürcher,c Sonia Borrell,a,b Marie Ballif,c Lukas Fenner,c Helen Cox,d Liliana K. Jane Carter,j Alash’le Abimiku,k Olivier Marcy,l,m Eduardo Gotuzzo,n Anchalee Avihingsanon,o Nicola Zetola,p Basra Doulla,q,r Erik C.

Clustering of the genome No Yes

Findings

History of TB disease No Yes