Multidrug efflux pump subunit AcrB (AcrB)

The Multidrug efflux pump subunit AcrB is the essential inner membrane component of the AcrAB-TolC system, the primary multidrug efflux pump in Gram-negative bacteria such as Escherichia coli (UniProt Consortium, 2023). It belongs to the Resistance-Nodulation-Division (RND) family and functions as a proton-motive force-dependent transporter that actively expels a wide variety of toxic compounds, including antibiotics, detergents, and dyes (Nikaido & Takatsuka, 2009). AcrB operates as a homotrimer, where each monomer cycles through three distinct conformational states—access, binding, and extrusion—to facilitate the peristaltic movement of substrates from the periplasm to the TolC exit duct (Yamaguchi et al., 2015). This efflux activity is a major driver of clinical multidrug resistance, as it prevents antibiotics like fluoroquinolones and beta-lactams from reaching their intracellular targets (Venter et al., 2015). Consequently, AcrB is a high-priority target for the development of efflux pump inhibitors (EPIs) like PAβN and D13-9001, which aim to restore antibiotic susceptibility (Nakashima et al., 2013). However, the development of these inhibitors faces challenges such as potential toxicity to host cells and the need for high potency to overcome the pump's high capacity (Opperman & Nguyen, 2015).

Other names

Acriflavine resistance protein BMultidrug transporter AcrBRND-type efflux pump AcrB

Efflux pump inhibition (EPI)