biostudies-literatureUshtanit AMinistry of Science and Higher Education of the Russian Federation1243https://www.ebi.ac.uk/biostudies/studies/S-EPMC8532644biostudies-literatureUnknown10(10)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. We determined the linezolid MICs for clinical isolates from the Moscow region and identified mutations in rplC and rrl genes. 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. 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.Antibiotics (Basel, Switzerland)Genetic Profile of Linezolid-Resistant M. tuberculosis Clinical Strains from Moscow.PMC8532644075-15-2019-1660Ushtanit AMikhailova YMakarova MSafonova SFilippov ALyubimova ABorisov SZimenkov DfalseGenetic Profile of Linezolid-Resistant M. tuberculosis Clinical Strains from Moscow.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. We determined the linezolid MICs for clinical isolates from the Moscow region and identified mutations in rplC and rrl genes. 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. 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.2021-01-01T00:00:00Z2021 Oct2024-11-08T11:39:06.917Z2024-11-08T11:39:06.917ZS-EPMC85326443468082310.3390/antibiotics10101243