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. Author manuscript; available in PMC: 2023 May 19.
Published in final edited form as: Cell Chem Biol. 2021 Nov 23;29(5):854–869.e9. doi: 10.1016/j.chembiol.2021.11.004

Figure 7. TP disrupts protein folding in mycobacterial cells, leading to increased sensitivity to stress and reduced frequencies of drug resistance.

Figure 7.

(A) Recovery of indicated Msm strains following heat shock prior to growth +/− TP at 37 °C or 40 °C indicates that cells lacking dnaJ1 are the most sensitive to TP following global protein denaturation. WT: Msm; ΔJ1: Msm ΔdnaJ1; ΔJ2: Msm ΔdnaJ2; Δ: heat shock; in: input. (B) Time course of denatured luciferase reactivation by indicated chaperone mixtures demonstrates DnaJ2 reactions are more sensitive to TP than DnaJ1 reactions. (C) TP exhibits a dose-dependent inhibition of chaperone network, whereas BC shows negligible inhibition. (D) Minimum inhibitory concentration (MIC) experiments in Msm show that addition of non-lethal concentrations of TP enhance the potency of aminoglycoside antibiotics. (E) While TP does not affect the activity of rifampicin (RIF) (left), addition of TP lowers the frequency of resistance (FOR) of Msm exposed to high levels of RIF (n = 6, lines indicate the median). ****p<0.0001 (Paired t-test was used for comparison). Error bars represent SD (typically n=3, except where otherwise indicated). See also Figure S7 and Table S7.