Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York
| Autor: | Jennifer L. Rakeman, Joseph Shea, Felicia Dworkin, Herns A. Modestil, Cheryl H. Kearns, Vincent E. Escuyer, Tanya A. Halse, Pascal Lapierre, Donna Kohlerschmidt, Kimberlee A. Musser |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Whole genome sequencing Genetics biology biochemical phenomena metabolism and nutrition Gene mutation bacterial infections and mycoses biology.organism_classification rpoB DNA sequencing Mycobacterium tuberculosis Genotype polycyclic compounds bacteria Mycobacteria growth indicator tube Genotyping |
| Zdroj: | Journal of Clinical Microbiology. 59 |
| ISSN: | 1098-660X 0095-1137 |
| Popis: | Rapid and reliable detection of rifampin (RIF) resistance is critical for the diagnosis and treatment of drug-resistant and multi-drug resistant (MDR) tuberculosis. Discordant RIF phenotype/genotype susceptibility results remain a challenge due to the presence of rpoB mutations which do not confer high levels of RIF resistance as have been exhibited in strains with mutations such as Ser450Leu. These strains, termed low-level RIF resistant, exhibit elevated RIF minimum inhibitory concentrations (MICs) compared to fully susceptible strains, however remain phenotypically susceptible by mycobacteria growth indicator tube (MGIT) testing and have been associated with poor patient outcomes. Here we assess RIF resistance prediction by whole-genome sequencing (WGS) among a set of 1779 prospectively tested strains by both prevalence of rpoB gene mutation and phenotype as part of routine clinical testing during a 21/2-year period. During this time, 139 strains were found to have nonsynonymous rpoB mutations, 53 of which were associated with RIF resistance, including both low-level and high-level resistance. Resistance to RIF (1.0 μg/mL in MGIT) was identified in 43 (81.1%) isolates. The remaining 10 (18.9%) strains were susceptible by MGIT, however were confirmed to be low-level RIF resistant by MIC testing. Full rpoB gene sequencing overcame the limitations of critical concentration phenotyping, probe-based genotyping, and partial-gene sequencing methods. Universal clinical WGS with concurrent phenotypic testing provided a more complete understanding of the prevalence and type of rpoB mutations and their association with RIF resistance in New York. |
| Databáze: | OpenAIRE |
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