BACILLUS-LICHENIFORMIS BACITRACIN-RESISTANCE ABC TRANSPORTER - RELATIONSHIP TO MAMMALIAN MULTIDRUG-RESISTANCE

The nucleotide sequence of the Bacillus licheniformis bacitracin-resis tance locus was determined. The presence of three open reading frames, bcrA, bcrB and bcrC, was revealed. The BcrA protein shares a high deg ree of homology with the hydrophilic ATP-binding components of the ABC family of transport proteins. The bcrB and bcrC genes were found to e ncode hydrophobic proteins, which may function as membrane components of the permease. Apart from Bacillus subtilis, these genes also confer resistance upon the Gram-negative Escherichia coli. The presumed func tion of the Bcr transporter is to remove the bacitracin molecule from its membrane target, In addition to the homology of the nucleotide-bin ding sites, BcrA protein and mammalian multidrug transporter or P-glyc oprotein share collateral detergent sensitivity of resistant cells and possibly the mode of Bcr transport activity within the membrane. The advantage of the resistance phenotype of the Bcr transporter was used to construct deletions within the nucleotide-binding protein to determ ine the importance of various regions in transport.