Multifaceted roles of efflux proteins in prokaryotes

Multidrug resistance is a globally increasing problem that has become an alarming threat to antibiotic therapy. A principal resistance mechanism that prokaryotic organisms have evolved is active multidrug efflux, whereby antibiotics and other xenobiotics are exported to the external environment by transport proteins in the cell membrane. Such proteins are especially abundant in Gram-negative bacteria that are responsible for a large proportion of hospital-acquired infections. Based on amino acid sequence similarity, substrate specificity and the energy source used for exporting substrates, prokaryotic organisms contain seven major families of distinct multidrug efflux transporters (ABC, MFS, RND, SMR, MATE, AbgT, PACE). Efflux proteins also have roles in biofilm formation, quorum sensing, resistance to heavy metals and biocides, cell homeostasis and in bacterial pathogenicity and virulence. Prokaryotic efflux proteins are therefore highly important targets for advancements in antibiotic therapy and for ongoing experimental characterisation of their structures, functions, molecular mechanisms and regulation.