Cell wall stress responses in Bacillus subtilis: the regulatory network of the bacitracin stimulon

Summary In response to sublethal concentrations of antibiotics, bacteria often induce an adaptive response that can contribute to antibiotic resistance. We report the response of Bacillus subtilis to bacitracin, an inhibi- tor of cell wall biosynthesis found in its natural envi- ronment. Analysis of the global transcriptional profile of bacitracin-treated cells reveals a response orches- trated by two alternative s s s factors ( s B and s M ) and three two-component systems (YvqEC, YvcPQ and BceRS). All three two-component systems are located next to target genes that are strongly induced by bacitracin, and the corresponding histidine kinases share an unusual topology: they lack about 100 amino acids in their extracellular sensing domain, which is almost entirely buried in the cytoplasmic membrane. Sequence analysis indicates that this novel N- terminal sensing domain is a characteristic feature of a subfamily of histidine kinases, found almost entirely in Gram-positive bacteria and frequently linked to ABC transporters. A systematic mutational analysis of bacitracin-induced genes led to the identification of a new bacitracin-resistance determinant, bceAB , encoding a putative ABC transporter. The bcrC baci- tracin resistance gene, which is under the dual con- trol of s s