Genetic Profile of Linezolid-Resistant <i>M. tuberculosis</i> Clinical Strains from Moscow
Anastasia Ushtanit,
Yulia Mikhailova,
Alexandra Lyubimova,
Marina Makarova,
Svetlana Safonova,
Alexey Filippov,
Sergey Borisov,
Danila Zimenkov
Affiliations
Anastasia Ushtanit
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
Yulia Mikhailova
The Moscow Research and Clinical Center for Tuberculosis Control, Moscow Government Health Department, 107014 Moscow, Russia
Alexandra Lyubimova
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
Marina Makarova
The Moscow Research and Clinical Center for Tuberculosis Control, Moscow Government Health Department, 107014 Moscow, Russia
Svetlana Safonova
The Moscow Research and Clinical Center for Tuberculosis Control, Moscow Government Health Department, 107014 Moscow, Russia
Alexey Filippov
The Moscow Research and Clinical Center for Tuberculosis Control, Moscow Government Health Department, 107014 Moscow, Russia
Sergey Borisov
The Moscow Research and Clinical Center for Tuberculosis Control, Moscow Government Health Department, 107014 Moscow, Russia
Danila Zimenkov
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
Background: Linezolid, bedaquiline, and newer fluoroquinolones are currently placed as priority Group A drugs for the treatment of drug-resistant tuberculosis. The number of reported linezolid-resistant clinical strains is still low, and the correlation of molecular determinants with phenotype is not perfect. Methods: We determined the linezolid MICs for clinical isolates from the Moscow region and identified mutations in rplC and rrl genes. Results: All 16 linezolid-resistant isolates had previously reported mutations in the rplC or rrl loci, and 13 of them bore a RplC C154R substitution. Detection of this substitution in a heteroresistant state was not successful, probably, due to the more stable DNA secondary structure of the mutated fragment, which precludes its amplification in mixes with the wild-type DNA. Strains with an rplC mutation had higher linezolid MIC compared to isolates with rrl mutations. Conclusions: Linezolid resistance mostly emerged during treatment with the latest regimen. Three primary cases with linezolid resistance question the possible transmission of totally drug-resistant tuberculosis in the Moscow region, which demands further investigation.
