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Rapidly Correcting Frameshift Mutations in the Mycobacterium tuberculosis orn Gene Produce Reversible Ethambutol Resistance and Small-Colony-Variant Morphology

Title: Rapidly Correcting Frameshift Mutations in the Mycobacterium tuberculosis orn Gene Produce Reversible Ethambutol Resistance and Small-Colony-Variant Morphology
Authors: Safi, Hassan; Lingaraju, Subramanya; Ma, Shuyi; Husain, Seema; Hoque, Mainul; Soteropoulos, Patricia; Rustad, Tige; Sherman, David R.; Alland, David
Contributors: HHS | NIH | National Institute of Allergy and Infectious Diseases
Source: Antimicrobial Agents and Chemotherapy ; volume 64, issue 9 ; ISSN 0066-4804 1098-6596
Publisher Information: American Society for Microbiology
Publication Year: 2020
Description: We have identified a previously unknown mechanism of reversible high-level ethambutol (EMB) resistance in Mycobacterium tuberculosis that is caused by a reversible frameshift mutation in the M. tuberculosis orn gene. A frameshift mutation in orn produces the small-colony-variant (SCV) phenotype, but this mutation does not change the MICs of any drug for wild-type M. tuberculosis . However, the same orn mutation in a low-level EMB-resistant double embB-aftA mutant (MIC = 8 μg/ml) produces an SCV with an EMB MIC of 32 μg/ml.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1128/aac.00213-20
DOI: 10.1128/AAC.00213-20
Availability: https://doi.org/10.1128/aac.00213-20; https://journals.asm.org/doi/pdf/10.1128/AAC.00213-20
Rights: https://journals.asm.org/non-commercial-tdm-license
Accession Number: edsbas.999262B7
Database: BASE