Molecule Information

General Information of the Molecule (ID: Mol01080)

• Name: Sensor protein kinase WalK (WALK) ,Staphylococcus aureus
• Synonyms: vicK; yycG
• Molecule Type: Protein
• Gene Name: walK
• Sequence:
  CTVILGFFIARTITKPITDMRNQTVEMSRGNYTQRVKIYGNDEIGELALAFNNLSKRVQE
  AQANTESEKRRLDSVITHMSDGIIATDRRGRIRIVNDMALKMLGMAKEDIIGYYMLSVLS
  LEDEFKLEEIQENNDSFLLDLNEEEGLIARVNFSTIVQETGFVTGYIAVLHDVTEQQQVE
  RERREFVANVSHELRTPLTSMNSYIEALEEGAWKDEELAPQFLSVTREETERMIRLVNDL
  LQLSKMDNESDQINKEIIDFNMFINKIINRHEMSAKDTTFIRDIPKKTIFTEFDPDKMTQ
  VFDNVITNAMKYSRGDKRVEFHVKQNPLYNRMTIRIKDNGIGIPINKVDKIFDRFYRVDK
  ARTRKMGGTGLGLAISKEIVEAHNGRIWANSVEGQGTSIFITLPCEVIEDGDWDE
• Function: Member of the two-component regulatory system WalK/WalR that regulates genes involved in cell wall metabolism, virulence regulation, biofilm production, oxidative stress resistance and antibiotic resistance via direct or indirect regulation of autolysins. Functions as a sensor protein kinase which is autophosphorylated at a histidine residue in the dimerization domain and transfers its phosphate group to the conserved aspartic acid residue in the regulatory domain of WalR. In turn, WalR binds to the upstream promoter regions of the target genes to positively and negatively regulate their expression.
• Uniprot ID: WALK_STAAU

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Staphylococcaceae
Genus: Staphylococcus
Species: Staphylococcus aureus

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Daptomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bacterial infection [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.S221P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MW2; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1616; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1617; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1618; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CiproR; 1242971
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The exact mechanism by which the changes in YycG alter the protein's function is not known. Martin et al. suggested that yycF and yycG are involved in cell permeability and showed that loss of yycF activity results in increased susceptibility to macrolide and lincosamide antibiotics and unsaturated long-chain fatty acids.

Disease Class: Bacterial infection [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.R263C
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MW2; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1616; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1617; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1618; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CiproR; 1242971
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The exact mechanism by which the changes in YycG alter the protein's function is not known. Martin et al. suggested that yycF and yycG are involved in cell permeability and showed that loss of yycF activity results in increased susceptibility to macrolide and lincosamide antibiotics and unsaturated long-chain fatty acids.

Disease Class: Bacterial infection [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; c.26121insA
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MW2; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1616; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1617; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CB1618; 1242971
• In Vitro Model: Staphylococcus aureus MW2-CiproR; 1242971
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The exact mechanism by which the changes in YycG alter the protein's function is not known. Martin et al. suggested that yycF and yycG are involved in cell permeability and showed that loss of yycF activity results in increased susceptibility to macrolide and lincosamide antibiotics and unsaturated long-chain fatty acids.

References

• Ref 1: Genetic changes that correlate with reduced susceptibility to daptomycin in Staphylococcus aureus. Antimicrob Agents Chemother. 2006 Jun;50(6):2137-45. doi: 10.1128/AAC.00039-06.
• Ref 2: Additional routes to Staphylococcus aureus daptomycin resistance as revealed by comparative genome sequencing, transcriptional profiling, and phenotypic studies. PLoS One. 2013;8(3):e58469. doi: 10.1371/journal.pone.0058469. Epub 2013 Mar 15.