The YheI/YheH heterodimer from Bacillus subtilis is a multidrug ABC transporter.

摘要: ABC (ATP-binding cassette) transporters form the largest family of membrane proteins in micro-organisms where they are able to transport a wide variety substrates against concentration gradient, an ATP-dependent process. Two genes from same putative Bacillus subtilis operon, yheI and yheH, encoding possibly two different transporters, were overexpressed Escherichia coli high yield, either separately or jointly. Using vesicles, it is shown here that both subunits required detect, (i) four structurally unrelated drugs, (ii) vanadate-sensitive ATPase activity. Mutation invariant Walker-A lysine alanine residue led inactive transporter. Moreover, after solubilization by detergent, wild-type co-purified on Ni-Agarose affinity column while only YheH subunit contained hexa-histidine tag. This shows YheI indeed interact together heterodimer. Importantly, expression yheH B. could be strongly stimulated addition sub-inhibitory concentrations various antibiotics. Therefore, YheI/YheH forms new heterodimeric multidrug transporter involved multiple antibiotic resistance vivo.