Abstract
The rise of antibiotic resistant bacteria requires unconventional strategies toward efficient chemotherapeutic agents, preferably with alternative mechanisms of action. The bacterial cell membrane has become an appealing target since its essential and highly conservative structure are key challenges to resistance mechanisms. Inspired by natural antimicrobial peptides, research on membrane-targeting antimicrobials has been growing out of the peptide space. The pursuit of more druggable molecules led to the discovery that the pharmacophore of antimicrobial peptides is smaller than anticipated. Several promising classes of membrane-targeting antimicrobials have been discovered, such as ceragenins, reutericyclines, carbohydrate amphiphiles – among others. This review will discuss the most recent findings on membrane-targeting antibiotics, focusing on small molecules outside the antimicrobial peptide molecular space.
Graphical abstract
Financial & competing interests disclosure
The European Union is gratefully acknowledged for the support of the project ‘Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease’ (D3i4AD; grant number FP7-PEOPLE-2013-IAPP, GA 612347). Fundação para a Ciência e a Tecnologia is also acknowledged for the support of project UID/Multi/0612/2013, and for the PhD grant co-sponsored by (grant number CIPAN SFRH/BDE/51998/2012 [CD]). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.