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. 2019 Mar 18;5(6):1001–1012. doi: 10.1021/acsinfecdis.9b00048

Figure 8.

Figure 8

Effect of SQ109, BM212, THPP1, AU1235, NITD-304, and NITD-349 on the membrane potential (ΔΨ) and electrochemical proton gradient (ΔpH) of intact Mtb bacilli. (A) Effect of inhibitors on ΔΨ (A) and ΔpH (B) of intact Mtb cells. The ΔΨ and inner bacterial pH of Mtb cells treated with DMSO and water (solvent controls; brown bars), control antibiotics (isoniazid, rifampicin, and ciprofloxacin), PMF dissipaters (valinomycin, nigericin, and CCCP), or the MmpL3 inhibitors SQ109, THPP1, AU1235, NITD-304, and NITD-349 at 4× and 20× their MIC value were determined. For solubility reasons, BM212 and nigericin were tested at 2× and 8× their MIC value (MIC values: NITD-304, 0.02 μM; NITD-349, 0.05 μM; SQ109, 2.36 μM; AU1235, 0.48 μM; BM212, 3.76 μM; THPP1, 13.44 μM; INH, 0.58 μM; RIF, 0.19 μM; nigericin, 4.31 μM; CCCP, 6.25 μM). Green bars are for the 2× and 4× MIC treatments; gray bars are for the 8× or 20× MIC treatments. Results are representative of three independent tests. The values represent the averages and standard deviations of measurements performed on three independent bacterial suspensions after exposure to the test compounds or solvents for 30 min at 37 °C. Asterisks denote statistically significant differences between water or DMSO controls and inhibitor-treated cells pursuant to the Student’s t-test (P < 0.05).