Targeting the energy-coupling factor (ECF) transporters: identification of new tool compounds

01 December 2021, Version 2


The energy-coupling factor (ECF) transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Their central role in the metabolism of bacteria and absence in humans make the ECF transporters a potential antibacterial target, which can be further investigated making use of a selective chemical probe. Here, we report on the virtual screening, design, synthesis, structure–activity relationships (SARs) and coarse-grained molecular dynamics simulations of the first class of inhibitors of the ECF transporters. We investigated the mechanism of action of this chemical class and profiled the best hit compounds regarding their pharmaceutical properties. The optimized hit has a minimum inhibitory concentration (MIC) value of 2 µg/mL against Streptococcus pneumoniae, which opens up the possibility to use this chemical class to investigate the role of the ECF transporters in health and disease.


energy-coupling factor transporter
Antibacterial activities
structure-activity relationship study
transmembrane protein structure

Supplementary materials

SI Discovery of antibacterial agents inhibiting the energy-coupling factor (ECF) transporters by structure-based virtual screening
The SI contains the description of the experiments performed in this study


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