Waste or die: The price to pay to stay alive.

Microorganisms need to constantly exchange with their habitat to capture nutrients and expel toxic compounds. The ATP-binding cassette (ABC) transporters, a family of membrane proteins especially abundant in microorganisms, are at the core of these processes. Due to their extraordinary ability to expel structurally unrelated compounds, some transporters play a protective role in different organisms. Yet, the downside of these multidrug transporters is their entanglement in the resistance to therapeutic treatments. Intriguingly, some multidrug ABC transporters show a high level of ATPase activity, even in the absence of transported substrates. Although this basal ATPase activity might seem a waste, we surmise that this inherent capacity allows multidrug transporters to promptly translocate any bound drug before it penetrates into the cell. Many ATP-binding cassette (ABC) transporters display a basal ATPase activity in the absence of transported substrates. Multidrug ABC exporters function according to an alternating access mechanism between inward- and outward-facing conformations. The basal ATPase activity of microbial multidrug ABC exporters is often either not or poorly stimulated by the presence of drugs. The sole binding of drugs to multidrug ABC exporters does not produce a major conformational change. When drugs stimulate the ATPase activity, they likely shift the equilibrium toward the outward-facing conformation of multidrug ABC exporters, a conformation prone to drug release. [ABSTRACT FROM AUTHOR]