Characteristic exploration of Mycobacterium tuberculosis isolated from patients with linezolid-treated multidrug-resistant tuberculosis.

SYNOPSIS: OBJECTIVES: Linezolid (LZD) is crucial for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB); however, mutations related to LZD resistance still need to be characterised. This study investigated resistance-related mutations on a whole-genome scale in clinical isolates from patients with MDR/XDR TB who failed LZD treatment.

METHODS: The phenotypic drug susceptibility test (DST) of first- and second-line anti-tuberculosis drugs was determined using the Sensititre™ plate; the Resazurin Microtitre Assay settled the minimal inhibitory concentration (MIC) of LZD. Overall, 25 sequential isolates previously collected and deposited in the Masan National TB Hospital (MNTH) Biobank were used. All included patients had MDR/XDR TB with failed LZD-included treatment. All isolates were subjected to whole-genome sequencing using the Illuminaplatform.

RESULTS: Of the 25 isolates, 18 were LZD resistant at the lowest MICs ≥ 1 mg/L and showed LZD resistance after 3 months of treatment; 20 had mutations in the rplC or rrl genes; 4 had G2814T mutations in rrl. 11 isolates harboured the T460C mutation in rplC. The G2814T mutant in rrl or the T460C mutant in rplC were resistant to LZD MICs up to 8 mg/L. One linezolid-resistant isolate harboring G2814T and T460C mutations exhibited MIC values greater than 16 mg/L. Conversely, seven isolates did not exhibit genetic mutations in rrl or rplC. Significant mutations or changes were observed when sequential isolates from the same patient were compared.

CONCLUSIONS: The study findings demonstrate mutations related to LZD resistance, which can aid in the detection of LZD resistance and optimisation of treatment regimens for patients with LZD-treated MDR/XDR TB.