Evolution of Multidrug Resistance during Staphylococcus aureus Infection Involves Mutation of the Essential Two Component Regulator WalKR
(A) Schematic figure of the walKR operon showing protein domains and positions of identified mutations. Protein domains were defined according to Dubrac et al . White regions of walK represent membrane spanning regions. (B) Amino acid sequences of the walR and walK genes. Domains are highlighted in color according to figure 1A. Identified mutations are indicated in bold type with an asterix. Membrane spanning regions of walK are italicized. The walR aspartic acid that is phosphorylated by walK and the walK histidine in the HisKA domain that is autophosphorylated are shown by arrows. Conserved regions are underlined and referred to in the text. (C) Ribbon diagram of the DNA binding domain of a WalR monomer from VISA strain JKD6005 (pink) modelled against the 1.87 Å structure of the WalR DNA-binding domain (PDB: 2ZXJ) from VSSA Staphylococcus aureus (blue). Shown is the position of the substituted amino acid (K->R) near the critical α3–β5 DNA binding loop (indicated by the arrow).