RESUMO
Mycobacterium tuberculosis (MTB) is known for its adaptive capability in developing resistance to antibiotics, through the selection of spontaneous mutations that arise during treatment. Generating spontaneous antibiotic-resistant mutants in vitro is challenging but necessary for studying this phenomenon. A protocol was designed and tested to select stable, MTB spontaneous, d-cycloserine (DCS) resistant mutants. Twenty-four colonies resistant to DCS were selected, demonstrating an increase between 1 and 4 times the Minimum Inhibitory Concentration (MIC) set for Mycobacterium tuberculosis H37Rv ATCC 27294 reference strain.
RESUMO
IQG-607 is a metal complex previously reported as a promising anti-tuberculosis (TB) drug against isoniazid (INH)-resistant strains of Mycobacterium tuberculosis Unexpectedly, we found that INH-resistant clinical isolates were resistant to IQG-607. Spontaneous mutants resistant to IQG-607 were subjected to whole-genome sequencing, and all sequenced colonies carried alterations in the katG gene. The katG(S315T) mutation was sufficient to confer resistance to IQG-607 in both MIC assays and inside macrophages. Moreover, overexpression of the InhA(S94A) protein caused IQG-607's resistance.