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AcrAB−TolC, a major efflux pump in Gram negative bacteria: toward understanding its operation mechanism

Antibiotic resistance (AR) is a silent pandemic that kills millions worldwide. Although the development of new therapeutic agents against antibiotic resistance is in urgent demand, this has presented a great challenge, especially for Gram-negative bacteria that have inherent drug-resistance mediated...

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Detalles Bibliográficos
Autor principal: Jang, Soojin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315565/
https://www.ncbi.nlm.nih.gov/pubmed/37254571
http://dx.doi.org/10.5483/BMBRep.2023-0070
Descripción
Sumario:Antibiotic resistance (AR) is a silent pandemic that kills millions worldwide. Although the development of new therapeutic agents against antibiotic resistance is in urgent demand, this has presented a great challenge, especially for Gram-negative bacteria that have inherent drug-resistance mediated by impermeable outer membranes and multidrug efflux pumps that actively extrude various drugs from the bacteria. For the last two decades, multidrug efflux pumps, including AcrAB−TolC, the most clinically important efflux pump in Gram-negative bacteria, have drawn great attention as strategic targets for re-sensitizing bacteria to the existing antibiotics. This article aims to provide a concise overview of the AcrAB−TolC operational mechanism, reviewing its architecture and substrate specificity, as well as the recent development of AcrAB−TolC inhibitors.