Energy-Coupling Factor Transporters as Novel Antimicrobial Targets

Spyridon Bousis, Inda Setyawati, Eleonora Diamanti, Dirk J. Slotboom, Anna K. H. Hirsch*

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number1800066
Number of pages17
JournalAdvanced Therapeutics
Volume2
Issue number2
DOIs
Publication statusPublished - Feb-2019

Keywords

  • antimicrobials
  • B-type vitamins
  • energy-coupling factor transporters
  • S-components
  • uptake
  • STAPHYLOCOCCUS-AUREUS INFECTIONS
  • ATP-BINDING
  • FOLIC-ACID
  • ECF TRANSPORTER
  • S-COMPONENT
  • COENZYME-A
  • CONFORMATIONAL-CHANGES
  • THIAMIN BIOSYNTHESIS
  • VANCOMYCIN-RESISTANT
  • COMPARATIVE GENOMICS

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