Fig. 6: Collateral vulnerabilities translate to clinically relevant INHR genotypes. | Nature Communications

Fig. 6: Collateral vulnerabilities translate to clinically relevant INHR genotypes.

From: Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis

Fig. 6

a, b Susceptibility of M. tuberculosis H37RV, INHR-KatGM225R and INHR-KatGW351G to inhibition by BDQ and LZD. Growth of M. tuberculosis was determined using REMA assay. c–e Susceptibility of M. tuberculosis DS-parent, INHR-katG, INHR-KatGS315N and a MDR- KatGS315N strain to inhibition and killing by (c) isoniazid and (d, e) bedaquiline. MIC and MBC assays are mean ± extrema of two biological replicates, n = 2 independent experiments. For MBC assays Inoc denotes the starting CFU/ml and no-cpd denotes the detected CFU/ml in the absence of ATc. The dashed line represents the lower limit of detection. For c–e all strains contain the chromosomally integrated plasmid pKM427 that is used as part of mycobacterial recombineering. The BDQ MIC is 0.2 µM as determined in d). f Susceptibility of INH sensitive and resistant clinical isolates to LZD The INHS isolate is TDR-TB 77, whilst INHR isolate is TDR-TB 42. Both strains are from the TDR-TB strain bank46. Source data are provided as a Source Data file.

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