New Multidrug Efflux Inhibitors for Gram-Negative Bacteria
Robert L. Marshall, Georgina S. Lloyd, Amelia J. Lawler, Sarah J. Element, Jaswant Kaur, Maria Laura Ciusa, Vito Ricci, Andreas Tschumi, Holger Kühne, Luke J. Alderwick, Laura J. V. Piddock
Abstract
Multidrug-resistant Gram-negative bacteria pose a serious threat to human and animal health. Molecules that inhibit multidrug efflux offer an alternative approach to resolving the challenges caused by antibiotic resistance, by potentiating the activity of old, licensed, and new antibiotics. We have developed, validated, and implemented a high-throughput screen and used it to identify efflux inhibitors from two compound libraries selected for their high chemical and pharmacological diversity. We found that the new high-throughput screen is a valuable tool to identify efflux inhibitors, as evidenced by the 43 new efflux inhibitors described in this study.