Mutations in MexB that affect the efflux of antibiotics with cytoplasmic targets

FEMS Microbiology Letters
Thelma Ohene-AgyeiHenrietta Venter

Abstract

Drug efflux pumps such as MexAB-OprM from Pseudomonas aeruginosa confer resistance to a wide range of chemically different compounds. Within the tripartite assembly, the inner membrane protein MexB is mainly responsible for substrate recognition. Recently, considerable advances have been made in elucidating the drug efflux pathway through the large periplasmic domains of resistance-nodulation-division (RND) transporters. However, little is known about the role of amino acids in other parts of the protein. We have investigated the role of two conserved phenylalanine residues that are aligned around the cytoplasmic side of the central cavity of MexB. The two conserved phenylalanine residues have been mutated to alanine residues (FAFA MexB). The interaction of the wild-type and mutant proteins with a variety of drugs from different classes was investigated by assays of cytotoxicity and drug transport. The FAFA mutation affected the efflux of compounds that have targets inside the cell, but antibiotics that act on cell wall synthesis and membrane probes were unaffected. Combined, our results indicate the presence of a hitherto unidentified cytoplasmic-binding site in RND drug transporters and enhance our understanding of the molecu...Continue Reading

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Citations

Jun 11, 2015·Biological Chemistry·Reinke Tobias Müller, Klaas Martinus Pos
Sep 17, 2014·MicrobiologyOpen·Thelma Ohene-AgyeiHenrietta Venter
Dec 1, 2017·Scientific Reports·Cesar A LópezS Gnanakaran
Mar 20, 2015·Clinical Microbiology Reviews·Xian-Zhi LiHiroshi Nikaido
Mar 5, 2017·Essays in Biochemistry·Mohsen ArzanlouHenrietta Venter
Apr 30, 2020·Journal of Microbiology and Biotechnology·Zhenyue FengYudong Cui

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