Bacterial efflux systems, the first survival kit.

Antibiotic resistance is a major threat to public health, especially in the form of multidrug resistance. Gram-negative pathogens, such as $Pseudomonas aeruginosa$, are of particular concern. One of the first survival kit of Gram-negative bacteria is the active export of drugs out of the cell, mainly mediated by resistance-nodulation-division (RND) efflux pumps. They are complex molecular machines able to efficiently shuttle chemically different compounds out of the cell. A strategy to avoid their action should be based on a knowledge at molecular level of the functioning of the RND efflux systems. Computational methods are well suited to provide key insights thereon. In particular, our results outline molecular-level information that could help the rational design of new inhibitors and new antibiotics less susceptible to the efflux mechanism.