Acra

AcrA is the gene encoding a periplasmic adaptor protein that is a core component of the AcrAB-TolC multidrug efflux pump found in many Gram-negative bacteria, most notably Escherichia coli. The AcrAB-TolC pump comprises the inner membrane transporter AcrB, the periplasmic adaptor AcrA, and the outer membrane channel TolC, forming a conduit that expels substrates from the cytoplasm or periplasm to the outside. AcrA bridges AcrB and TolC and facilitates assembly and function of the tripartite complex, enabling export of a broad range of antibiotics, detergents, dyes, and toxic compounds. This activity contributes to intrinsic resistance and can be upregulated in response to antibiotic exposure.

Genetic regulation and expression: In many bacteria, acrA and acrB are co-regulated with tolC. Expression is repressed by AcrR and can be activated by stress-response regulators such as MarA, SoxS, and Rob, leading to increased efflux when needed.

Structure and localization: AcrA is a periplasmic protein exported via the Sec pathway and lacking a transmembrane segment; its elongated architecture supports interactions with both AcrB and TolC.

Clinical and research significance: The AcrAB-TolC system is a major contributor to multidrug resistance in Enterobacteriaceae. Disruption of acrA reduces efflux and increases antibiotic susceptibility in many strains. Researchers investigate inhibitors targeting AcrA, AcrB, or TolC to restore antibiotic efficacy.