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. Author manuscript; available in PMC: 2014 Dec 5.
Published in final edited form as: Cell. 2013 Dec 5;155(6):1296–1308. doi: 10.1016/j.cell.2013.10.045

Figure 5.

Figure 5

A. 6-FABA inhibits the growth of Mtb in 7H9. B. To test the bactericidal potential of 6-FABA, wild type Mtb was treated with 6-FABA in 7H9, and cultures were plated for CFU at various time points. C. Wild type (blue) and mutant (black) TrpE (F68I) were isolated and enzymatic activity was assessed by measuring chorismate concentration. D. The inhibitory affect of tryptophan on both wild type (blue) and mutant (black) TrpE was measured as % initial velocity of the no-inhibitor control reaction. E. Mtb TrpE structure (blue) was modeled based on the homologous enzyme from S. macrcescens (beige), showing F68 in the allosteric binding pocket of tryptophan.

C. Wild type Mtb was used to infect macrophages. On day 1 after infection, macrophages were treated with 6-FABA, and on day 5, cells were lysed and bacteria plated, showing the 6-FABA was bactericidal in macrophages. D. To test the synergy between 6-FABA and IFN-γ, we added 6-FABA and IFN-γ at concentrations that inhibited approximately half of bacterial growth. E. Together, their effect was greater than the estimated additive effect of the two molecules in the absence of synergy, showing that they indeed work synergistically to kill Mtb in macrophages.