Controlling bacterial infections by inhibiting proton-dependent processes.

Bacterial resistance to antibiotics is recognized as one of the greatest threats in modern healthcare, taking a staggering toll worldwide. New approaches for controlling bacterial infections must be designed, eventually combining multiple strategies for complimentary therapies. This review explores an old/new paradigm for multi-targeted antibacterial therapy, focused at disturbing bacterial cytoplasmic membrane functions at sub minimal inhibitory concentrations, namely through superficial physical alterations of the bilayer, thereby perturbing transmembrane signals transduction. Such a paradigm may have the advantage of fighting the infection while avoiding many of the known resistance mechanisms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.