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Evolution of Multidrug Resistance during Staphylococcus aureus Infection Involves Mutation of the Essential Two Component Regulator WalKR

Figure 5

Microarray transcriptional analysis of defined WalK (G223D) and WalR (K208R) mutants compared to parental strains.

(A) Results of microarray transcriptional analysis of TPS3130 (WalK G223D) and TPS3190 (WalR K208R) compared to respective parental strains. Up-regulated genes (in red) are differentially up-regulated in the mutants compared to the parent strains, and the down-regulated genes (in green) are differentially down-regulated in the mutant strains compared to parent strains. The heat map analysis highlights the proportion of each cluster of orthologous groups (COG) functional group [61] that is differentially regulated in the array analysis. This clearly demonstrates significant global transcriptional changes in the WalK and WalR mutant strains affecting genes from all COG groups, and providing a similar pattern of transcriptional response. (B) Schematic representation of the genes commonly transcribed in the two microarray experiments. A total of 163 genes were commonly transcribed, and the major up-regulated and down-regulated genes are highlighted. Note, # denotes loci which have been previously shown or are predicted to have upstream WalR binding domains [31], [32]; A, alanine; D, aspartate; E, glutamate; R, arginine; P, proline; V, valine; L, leucine; I, isoleucine.

Figure 5