Molecular epidemiology, genomics and evolution of Mycobacterium tuberculosis antibiotic resistance in Belarus, 2010–2013

Authors

• K Wollenberg
• C Desjardins
• A Zalutskaya
• V Slodovnikova
• M Quiñones
• A Oler
• T Abeel
• M Tartakovsky
• A Gabrielian
• S Hoffner
• A Rosenthal
• A Skrahin
• B Birren
• A Earl
• A Skrahina

Abstract

​The emergence and spread of Mycobacterium tuberculosis (M.tb) strains exhibiting resistance to many, if not all, available drugs are critical global health issues. Eastern Europe, and particularly countries of the former Soviet Union, has some of the highest incidence rates of drug-resistant (DR) M.tb. To better understand the mechanisms and epidemiology of M.tb drug resistance, we sequenced and analyzed the genomes of 137 M.tb isolated from patient samples between 2010 and 2013 in Minsk, Belarus with known antibiotic susceptibility profiles. Among our findings, we observed mutations in well-characterized drug resistance loci that explained the vast majority of phenotypic resistance in these samples, indicating that M.tb. in Belarus is not evolving drug resistance through novel mechanisms. Further, using a phylogenomic approach, we concluded that the majority of DR M.tb infections were due to recent transmission of already DR strains rather than repeated de novo evolution of resistance within patients. We also detected evidence for mixed infections, with some patients harboring at least two strains, often having discordant drug resistance genotypes. Finally, we observed distantly related strains in temporally distinct samplings from individual patients indicating that multiple rounds of infection can occur in patients, particularly among HIV+ patients.

Scientific Focus Area: Microbiology and Infectious Diseases

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