Revisiting activation of and the mechanism of resistance to the compound IQG-607 in Mycobacterium tuberculosis [PublishAheadOfPrint]

IQG-607 is a metal complex previously reported as a promising anti-TB drug against isoniazid (INH)-resistant strains of M. 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, overexpressing the InhA(S94A) protein caused IQG-607's resistance.

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