Energy‐Coupling Factor Transporters as Novel Antimicrobial Targets

In an attempt to find new antibiotics, novel ways of interfering with important biological functions should be explored, especially with those which are necessary or even irreplaceable for bacterial survival, growth, and virulence. The purpose of this review is to highlight B‐type vitamin transporters from the energy‐coupling factor (ECF) family, which are not present in humans, as potential antimicrobial targets. In addition, a druggability analysis of an ECF transporter for folic acid and sequence‐conservation studies in seven prominent pathogens revealed new druggable pockets. Evaluation of the presence of de novo biosynthetic routes for the vitamins in question in the seven pathogens confirmed that this target class holds promise for the discovery of antimicrobial drugs with a new mechanism of action, possibly on a broad‐spectrum level. Energy‐coupling factor transporters are novel antibacterial targets. This kind of transmembrane protein transports several vitamins into the cytosol according to an unprecedented mechanism and is found in bacterial pathogens but not in humans. Evidence suggests that inhibition of this uptake should diminish bacterial survival, setting the stage for the discovery of novel antibacterial agents with an unprecedented mechanism of action.