Cell envelope stress induced by the bacteriocin Lcn972 is sensed by the lactococcal two-component system CesSR

The non-pore-forming bacteriocin lactococcin 972 (Lcn972) inhibits the synthesis of peptidoglycan at the septum in Lactococcus lactis. In this work, the genome-wide response of L. lactis MG1614 to Lcn972 was analysed by DNA microarrays. We found 26 genes to be significantly upregulated. Most of these encode membrane proteins of unknown function and the two-component system (TCS) CesSR (formerly known as TCS-D). CesSR orchestrates the response of L. lactis to Lcn972. None of the genes upregulated in L. lactis MG1614 were induced by Lcn972 in L. lactis Delta cesR. In silico analysis of the promoter regions of the upregulated genes revealed a novel conserved 16 bp palindromic sequence at positions -73/-72 or -46 relative to the putative transcriptional start sites. Point mutations and deletion of this CesR box abolished regulation. Purified His-tagged CesR interacts in electrophoretic mobility shift assays with several promoters carrying the CesR box. The CesR box is also present in other Gram-positive cocci, upstream of genes involved in cell envelope stress. CesSR was strongly induced by lipid II-interacting cationic polypeptides and disruption of cesR increased susceptibility to these antimicrobials. We propose here that CesSR of L. lactis controls the immediate response to cell envelope stress in this organism.