Revisiting Activation of and Mechanism of Resistance to Compound IQG-607 in Mycobacterium tuberculosis.

Bruno Lopes AbbadiAnne D VillelaValnês S Rodrigues-JuniorFernanda T SubtilPedro F DalbertoAna P S PinheiroDiógenes S SantosPablo MachadoLuiz A BassoCristiano Valim Bizarro

Published in: Antimicrobial agents and chemotherapy (2018)

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.

Keyphrases

mycobacterium tuberculosis
pulmonary tuberculosis
escherichia coli
emergency department
high throughput
copy number
transcription factor
genome wide
dna methylation
gene expression
amino acid
drug induced