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walK

histidine kinase

NCBI Pathogen Isolates

Bacterial genomes carrying this gene

NCBI Reference Gene Catalog

Known alleles and reference sequences

Protein entries specific to walK

Browse AMR rules for walK

Validation StatusSupported

Overview

Mechanism: deletion mutation leading to loss of a single amino acid
Validation Method: introduction of the mutation into the parent strain and measurement of MIC
Drug Classes: Vancomycin, Daptomycin, Dalbavancin, Vancomycin|Daptomycin|Dalbavancin, CEF, DAPTOMYCIN, Penicillin, Vancomycin|Daptomycin, Cervimycin|Vancomycin, Methicillin
Organisms: Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Bacillus subtilis, L. monocytogenes, Staphylococcus haemolyticus
Geographic Location: Japan
Alleles: 2
Papers: 28
Databases: Reslit
Mutations: 35

Mutations

Protein Change	Nucleotide Change	Mechanism	Organism	Resistance To	Database	Validation Status
A567V	-	-	Staphylococcus aureus	Vancomycin\|Daptomycin\|DalbavancinDaptomycin	Reslit	Candidate
S437F	-	-	Staphylococcus aureus	Vancomycin	Reslit	Candidate
G223S	-	-	Staphylococcus aureus	Vancomycin

Allele Variants2

Allele	Database	Papers	Drug Classes	Organisms	Countries	Years	Sequence Accession	Protein Accession
walK	Reslit	6	Vancomycin, Daptomycin +1	Staphylococcus aureus +1	Japan	2011, 2015, 2019, 2021, 2023, 2024	AP019542\|AP019543\|AP019545	-
walk/R	Reslit	1	Vancomycin	Staphylococcus aureus +1	-	2021	-	-

Papers28

1

walK and clpP mutations confer reduced vancomycin susceptibility in Staphylococcus aureus.

PMID 21628539 · 2011

The study identifies walK and clpP mutations as contributing to reduced vancomycin susceptibility in Staphylococcus aureus, demonstrating that these mutations lead to increased vancomycin MIC when introduced into a susceptible strain.

Gene Information

Gene Name: walK
Allele: walK
Encodes: histidine kinase
Source Database: Reslit
Mechanism: deletion mutation leading to loss of a single amino acid
Confers Resistance To: Vancomycin
Organisms Tested In: • Staphylococcus aureus
Validation Method: introduction of the mutation into the parent strain and measurement of MIC

2

Impact of daptomycin resistance on Staphylococcus aureus virulence.

PMID 25830650 · 2015

Gene Information

Gene Name: walK
Allele: walK
Encodes: sensor histidine kinase
Source Database: Reslit
Mechanism: point mutation
Confers Resistance To: Daptomycin
Organisms Tested In: • Staphylococcus aureus
Validation Method: mutant analysis

3

IS256-Mediated Overexpression of the WalKR Two-Component System Regulon Contributes to Reduced Vancomycin Susceptibility in a Staphylococcus aureus Clinical Isolate.

PMID 31474962 · 2019

The study identifies mprF and dltABCD as key contributors to DAP resistance in S. aureus isolates, with a non-synonymous mutation in mprF (Trp 424 Cys) playing a significant role in increased DAP resistance.

Gene Information

Gene Name: walK
Allele: walK
Encodes: Sensor protein kinase WalK
Source Database: Reslit
Confers Resistance To: Vancomycin
Organisms Tested In: • Staphylococcus aureus
Geographic Location: Japan
Validation Method: RNA-Seq analysis showing >10-fold increased expression in KG-18 compared to KG-03
Sequence Accession: AP019542|AP019543|AP019545

4

Investigating the effect of an identified mutation within a critical site of PAS domain of WalK protein in a vancomycin-intermediate resistant Staphylococcus aureus by computational approaches.

PMID 34474665 · 2021

Gene Information

Gene Name: walK
Allele: walK
Encodes: sensor histidine kinase
Source Database: Reslit
Organisms Tested In: • Staphylococcus aureus

5

Antibiotic resistance alters through iron-regulating Sigma factors during the interaction of Staphylococcus aureus and Pseudomonas aeruginosa.

PMID 34531485 · 2021

The study shows that the interaction between S. aureus and P. aeruginosa influences antibiotic resistance through changes in the expression of genes such as kpc, mexA-mexB-oprM, oprD, norA, and walk/R, which are involved in carbapenem, ciprofloxacin, and vancomycin resistance.

Gene Information

Gene Name: walK
Allele: walk/R
Encodes: two-component system
Source Database: Reslit
Confers Resistance To: Vancomycin
Organisms Tested In: • Staphylococcus aureus
• Pseudomonas aeruginosa
Validation Method: expression level analysis

6

Emerging resistance in Staphylococcus epidermidis during dalbavancin exposure: a case report and in vitro analysis of isolates from prosthetic joint infections.

PMID 36611258 · 2023

Gene Information

Gene Name: walK
Allele: walK
Encodes: two-component system sensor kinase
Source Database: Reslit
Mechanism: mutation
Confers Resistance To: Dalbavancin
Organisms Tested In: • Staphylococcus epidermidis
Validation Method: whole genome sequencing

7

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

PMID 38997253 · 2024

The study describes the asymmetric total synthesis of polycyclic xanthenes and identifies compound 22 as a novel WalK activator with antibacterial activity against MRSA. Mutations in the walK gene were found to reduce susceptibility to 22.

Gene Information

Gene Name: walK
Allele: walK
Encodes: serine/threonine protein kinase
Source Database: Reslit
Mechanism: mutation in the walK gene leads to resistance
Organisms Tested In: • Staphylococcus aureus
Validation Method: generation of mutants through serial passaging and confirmation of resistance phenotype
Sequence Accession: PRJNA1052989|PRJNA1113534|PRJNA1113431