Bacitracins are mixtures of structurally related cyclic
polypeptides with
antibiotic properties. They act by interfering with the biosynthesis of the bacterial cell wall. In this study, we analyzed an avian necrotic
enteritis strain of Clostridium perfringens that was resistant to
bacitracin and produced NetB toxin. We identified a
bacitracin resistance locus that resembled a
bacitracin resistance determinant from Enterococcus faecalis. It contained the structural genes bcrABD and a putative regulatory gene, bcrR. Mutagenesis studies provided evidence that both bcrA and bcrB are essential for
bacitracin resistance, and that evidence was supported by the results of experiments in which the introduction of both the bcrA and bcrB genes into a
bacitracin-susceptible C. perfringens strain was required to confer
bacitracin resistance. The wild-type strain was shown to contain at least three large, putatively conjugative plasmids, and the bcrRABD locus was localized to an 89.7-kb plasmid, pJIR4150. This plasmid was experimentally shown to be conjugative and was sequenced. The sequence revealed that it also carries a tpeL toxin gene and is related to the pCW3 family of conjugative antibiotic resistance and toxin plasmids from C. perfringens. The bcr genes were located on a genetic
element, ICECp1, which is related to the Tn916 family of integrative conjugative elements (ICEs). ICECp1 appears to be the first Tn916-like
element shown to confer
bacitracin resistance. In summary, we identified in a toxin-producing C. perfringens strain a novel mobile
bacitracin resistance
element which was experimentally shown to be essential for
bacitracin resistance and is carried by a putative
ICE located on a conjugative plasmid.