Refutation: Spontaneous secondary mutations confound analysis of the essential two component system WalKR in Staphylococcus aureus

Ji et al.,1 recently detailed the structure of the extracytoplasmic Per-Arnt-Sim (PAS) domain of WalK (WalKEC-PAS), the sensor kinase of the essential two-component system WalKR in Staphylococcus aureus. The authors made two independent walK mutants in S. aureus, each with a single amino acid alteration in WalKEC-PAS. They postulated from comparative structural analysis and primary sequence comparisons that these residues might be important for extra cellular signal transduction. We have also been exploring the function of WalKR and were surprised by the striking phenotypic impact of a single amino acid substitutions in the WalK sensor, which were contrary to our own unpublished observations.\n\nThe authors subjected their WalKEC-PAS mutants (WalKD119A and WalKVl49A) to a series of phenotypic screens to probe the function of this domain. Compared to the parental methicillin sensiti ...