Chlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux Pump.

Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux is an encouraging strategy to restore the antibacterial activity of antibiotics. Chlorpromazine and amitriptyline have been shown to behave as efflux inhibitors.

Overexpression of RamA, Which Regulates Production of the Multidrug Resistance Efflux Pump AcrAB-TolC, Increases Mutation Rate and Influences Drug Resistance Phenotype.

In , the AcrAB-TolC efflux pump exports substrates, including antimicrobials, from the cell. Overexpression of AcrAB-TolC can occur after exposure to fluoroquinolones, leading to multidrug resistance. The expression of AcrAB-TolC in is primarily regulated by the transcriptional activator RamA.

Do phenothiazines possess antimicrobial and efflux inhibitory properties?

Antibiotic resistance is a global health concern; the rise of drug-resistant bacterial infections is compromising the medical advances that resulted from the introduction of antibiotics at the beginning of the 20th century. Considering that the presence of mutations within individuals in a bacterial population may allow a subsection to survive and propagate in response to selective pressure, as long as antibiotics are used in the treatment of bacterial infections, development of resistance is an inevitable evolutionary outcome. This, combined with the lack of novel antibiotics being released to the clinical market, means the need to develop alternative strategies to treat these resistant infections is critical.