Functional characterization of BcrR: a one-component transmembrane signal transduction system for bacitracin resistance.

摘要: Bacitracin is a cell wall targeting antimicrobial with clinical and agricultural applications. With the growing mismatch between resistance development, it essential we understand molecular mechanisms of in order to prioritize generate new effective antimicrobials. BcrR unique membrane-bound one-component system that regulates high-level bacitracin Enterococcus faecalis. In presence bacitracin, activates transcription bcrABD operon conferring through putative ATP-binding cassette (ABC) transporter (BcrAB). has three functional domains, an N-terminal helix-turn-helix DNA-binding domain, intermediate oligomerization domain C-terminal transmembrane domain. However, signal transduction remain unknown. Random mutagenesis bcrR was performed loss- gain-of-function mutants using transcriptional reporters fused target promoter PbcrA. Fifteen were isolated across all proposed comprising 14 loss-of-function one mutant. The variant (G64D) mapped dimerization BcrR, analyses indicated G64D mutant constitutively expresses PbcrA-luxABCDE reporter. membrane insertion not affected five chosen for further characterization. Homology modelling revealed roles two key residues (R11 S33) activation. Here present model activation transduction, providing valuable insight into characterization systems how they can coordinate critical bacterial responses, such as resistance.