Plant derived inhibitors of bacterial efflux pumps: an update

Ever increasing numbers of antibiotic resistances are putting more and more pressure on research and global health systems. Multidrug-resistant bacteria even escape from second-line antibiotics and only a few promising candidates are presently in the pipeline. Intrinsic resistance of bacteria mediated by efflux pumps play a crucial role in the development and implementation of resistances. Efflux pump inhibitors represent one possible way to overcome this decreasing sensitivity of bacteria to antibiotics. The co-administration of such efflux pump inhibitors together with an antibiotic reduces the amount needed of the antibiotic for the same therapeutic effect by cutting side effects. These inhibitors have also the possibility to reactivate ineffective antibiotics again for therapy. Plants are facing constant bacterial exposure and are therefore a promising source for new efflux pump inhibitors due to the enormous compound diversity, low toxicity and high tolerability. Reviewing the literature, we herein present an update of newly discovered efflux pump inhibitors with plant-based origin against bacterial strains of concern. Various compounds from 23 different plants have been reported and evaluated for their potential as efflux pump inhibitors based on efflux and accumulation data. This review also discusses the hurdles of clinical implementation.