E. coli Growth Inhibitory Assays under AnaerobicConditions. M. tuberculosis or S. aureus treated with the MenAinhibitors could not be rescued completely even at higherconcentrations of exogenous menaquinone (VK 2). In contrast,growth inhibition of E. coli by the MenA inhibitor could berescued by supplementation of VK2 (50 μM) under “anaerobicconditions” (vide supra). 46 E. coli growth inhibition rescued byaddition of VK2 may be attributed to the degree of permeabilityof VK 2 through the cell envelop. Although lack of activity ofMenA inhibitors against Gram-negative bacteria grown underaerobic conditions have been demonstrated, all MenAinhibitors identified in this program showed growth inhibitionof E. coli at 5−10 μg/mL concentrations under anaerobicconditions, and the inhibitory effect of MenA inhibitor wasrescued by supplementation of VK 2 . Therefore, theseconvenient cell-based assays using E. coli under anaerobicconditions can be utilized to confirm that the inhibitormolecules kill Gram-positive bacteria including Mtb bytargeting MenA biosynthesis or bacterial electron transportsystems
Question
E. coli Growth Inhibitory Assays under AnaerobicConditions. M. tuberculosis or S. aureus treated with the MenAinhibitors could not be rescued completely even at higherconcentrations of exogenous menaquinone (VK 2). In contrast,growth inhibition of E. coli by the MenA inhibitor could berescued by supplementation of VK2 (50 μM) under “anaerobicconditions” (vide supra). 46 E. coli growth inhibition rescued byaddition of VK2 may be attributed to the degree of permeabilityof VK 2 through the cell envelop. Although lack of activity ofMenA inhibitors against Gram-negative bacteria grown underaerobic conditions have been demonstrated, all MenAinhibitors identified in this program showed growth inhibitionof E. coli at 5−10 μg/mL concentrations under anaerobicconditions, and the inhibitory effect of MenA inhibitor wasrescued by supplementation of VK 2 . Therefore, theseconvenient cell-based assays using E. coli under anaerobicconditions can be utilized to confirm that the inhibitormolecules kill Gram-positive bacteria including Mtb bytargeting MenA biosynthesis or bacterial electron transportsystems
Solution
The passage discusses the results of E. coli growth inhibitory assays conducted under anaerobic conditions. It states that M. tuberculosis or S. aureus treated with MenA inhibitors could not be completely rescued even at higher concentrations of exogenous menaquinone (VK2). However, the growth inhibition of E. coli by the MenA inhibitor could be rescued by supplementing with VK2 at a concentration of 50 μM under anaerobic conditions.
The passage suggests that the ability of VK2 to rescue E. coli growth inhibition may be due to its permeability through the cell envelope. It also mentions that MenA inhibitors have been shown to be inactive against Gram-negative bacteria grown under aerobic conditions. However, all MenA inhibitors identified in this study demonstrated growth inhibition of E. coli at concentrations of 5-10 μg/mL under anaerobic conditions. Furthermore, the inhibitory effect of the MenA inhibitor could be rescued by supplementing with VK2.
Based on these findings, the passage suggests that convenient cell-based assays using E. coli under anaerobic conditions can be used to confirm that the inhibitor molecules target MenA biosynthesis or bacterial electron transport systems, thereby killing Gram-positive bacteria including Mtb.
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