The rise of antibiotic-resistant infections has been well documented and the need for novel antibiotics cannot be overemphasized. US FDA approved antibiotics target only a small fraction of bacterial cell wall or membrane components, well-validated antimicrobial targets. In this review, we highlight small molecules that inhibit relatively unexplored cell wall and membrane targets. Some of these targets include teichoic acids-related proteins (DltA, LtaS, TarG and TarO), lipid II, Mur family enzymes, components of LPS assembly (MsbA, LptA, LptB and LptD), penicillin-binding protein 2a in methicillin-resistant Staphylococcus aureus, outer membrane protein transport (such as LepB and BamA) and lipoprotein transport components (LspA, LolC, LolD and LolE). Inhibitors of SecA, cell division protein, FtsZ and compounds that kill persister cells via membrane targeting are also covered.
Keywords: antimicrobial resistance; cell membrane; cell wall; multidrug-resistant bacteria; new bacterial targets; small-molecule antimicrobials.