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clpP

proteolytic regulatory protein

NCBI Pathogen Isolates

Bacterial genomes carrying this gene

NCBI Reference Gene Catalog

Known alleles and reference sequences

Protein entries specific to clpP

Browse AMR rules for clpP

Validation StatusSupported

Overview

Mechanism: deletion mutation leading to inactivation
Validation Method: introduction of the mutation into the parent strain and measurement of MIC
Drug Classes: Vancomycin, Daptomycin, Oxacillin, Daptomycin|Vancomycin|Oxacillin
Organisms: Staphylococcus aureus, Saccharomyces cerevisiae, Escherichia coli, Escherichia coli K-12 MG1655, Staphylococcus pseudintermedius
Alleles: 2
Papers: 5
Databases: Reslit
Mutations: 2

Mutations

Protein Change	Nucleotide Change	Mechanism	Organism	Resistance To	Database	Validation Status
T6I	-	-	Staphylococcus pseudintermedius	Vancomycin	Reslit	Candidate
G94D	-	eliminates proteolytic activity of ClpP	Staphylococcus aureus	Daptomycin\|Vancomycin\|Oxacillin	Reslit	Candidate

Allele Variants2

Allele	Database	Papers	Drug Classes	Organisms	Countries	Years	Sequence Accession	Protein Accession
clpP	Reslit	3	Vancomycin, Daptomycin +1	Staphylococcus aureus +1	-	2011, 2021, 2023	PRJEB35347	-
CLPP	Reslit	1	-	Saccharomyces cerevisiae +2	-	2020	-	-

Papers5

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: clpP
Allele: clpP
Encodes: proteolytic regulatory protein
Source Database: Reslit
Mechanism: deletion mutation leading to inactivation
Confers Resistance To: Vancomycin
Organisms Tested In: • Staphylococcus aureus
Validation Method: introduction of the mutation into the parent strain and measurement of MIC

2

Imipridone Anticancer Compounds Ectopically Activate the ClpP Protease and Represent a New Scaffold for Antibiotic Development.

PMID 32094149 · 2020

The study identifies CLPP and MIPEP as critical genes involved in the resistance to imipridone compounds ONC201 and ONC212. These genes are part of the mitochondrial protease pathway and their disruption leads to resistance against these compounds.

Gene Information

Gene Name: clpP
Allele: CLPP
Encodes: protease
Source Database: Reslit
Organisms Tested In: • Saccharomyces cerevisiae
• Staphylococcus aureus
• Escherichia coli
Validation Method: CRISPR knockout screens and yeast-based surrogate genetic assays

3

Evolution of honey resistance in experimental populations of bacteria depends on the type of honey and has no major side effects for antibiotic susceptibility.

PMID 34025770 · 2021

The study found that bacteria adapted to certain honeys, particularly Manuka honey, through mutations in genes involved in detoxifying methylglyoxal. However, no evidence was found that honey adaptation conferred cross-resistance or collateral sensitivity against nine antibiotics.

Gene Information

Gene Name: clpP
Allele: clpP
Encodes: serine protease
Source Database: Reslit
Mechanism: mutated in multiple honey-evolved isolates
Organisms Tested In: • Escherichia coli K-12 MG1655
Validation Method: single-gene knockout experiments
Sequence Accession: PRJEB35347

4

A Clinically Selected Staphylococcus aureus clpP Mutant Survives Daptomycin Treatment by Reducing Binding of the Antibiotic and Adapting a Rod-Shaped Morphology.

PMID 37184389 · 2023

Inactivation of the ClpP protease in Staphylococcus aureus leads to reduced susceptibility to daptomycin, vancomycin, and oxacillin. A single nucleotide polymorphism (SNP) in the clpP gene (G281A) results in a G94D amino acid substitution, which inactivates ClpP and confers resistance. Additionally, a SNP in the rpoB gene (C1430A) leads to an A477D substitution, which confers resistance to rifampin.

Gene Information

Gene Name: clpP
Allele: clpP
Encodes: protease
Source Database: Reslit
Mechanism: inactivation of ClpP protease leads to reduced susceptibility to daptomycin, vancomycin, and oxacillin
Confers Resistance To: DaptomycinVancomycinOxacillin
Organisms Tested In: • Staphylococcus aureus
Validation Method: MIC testing and population analysis profiles