A highly rifampicin resistant Mycobacterium tuberculosis strain emerging in Southern Brazil

• Published in: bioRxiv
• Main Authors: Rossetti, Maria Lucia, Pedro Eduardo Almeida Da Silva, Richard Steiner Salvato, Reis, Ana Júlia, Schiefelbein, Sun Hee, Andrea Von Groll, Regina Bones Barcellos, Maschmann, Raquel, Esteves, Leonardo, Spies, Fernanda, Trespach, Rubia Raubach, Elis Regina Dalla Costa, Hermes Luís Neubauer De Amorim
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 03.09.2020
• Subjects: Binding sites; DNA-directed RNA polymerase; Drug resistance; Epidemiology; Genomics; Minimum inhibitory concentration; Mycobacterium tuberculosis; Nucleotides; Prisoners; Rifampin; RNA polymerase; RpoB protein; Tuberculosis; Whole genome sequencing; Brazil
• DOI: 10.1101/2020.09.03.282194

ABSTRACT Here we described phenotypical, molecular and epidemiological features of a highly rifampicin-resistant Mycobacterium tuberculosis strain emerging in Southern Brazil, that carries an uncommon insertion of 12 nucleotides at the codon 435 in the rpoB gene. Employing a whole-genome sequencing-based study on drug-resistant Mycobacterium tuberculosis strains, we identified this emergent strain in 16 (9.19%) from 174 rifampicin-resistant clinical strains included. Nine of these 16 strains were available to minimum inhibitory concentration determination and for all of them was found a high rifampicin-resistance level (≥ to 32 mg/L). This high resistance level could be explained by structural changes into the RIF binding site of RNA polymerase caused by the insertions, and consequent low-affinity interaction with rifampicin complex confirmed through protein modeling and molecular docking simulations. Epidemiological investigation showed that most of the individuals (56.25%) infected by the studied strains were prison inmate individuals or that spent some time in prison. The phylogenomic approach revealed that all strains carrying on the 12 nucleotide insertion belonged to the same genomic cluster, evidencing a communal transmission chain involving inmate individuals and community. We stress the importance of tuberculosis genomic surveillance and the introduction of measures to interrupt the Mycobacterium tuberculosis transmission chain in this region. Competing Interest Statement The authors have declared no competing interest.