Browse AMR Genes

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cls

cardiolipin synthetase

NCBI Pathogen Isolates

Bacterial genomes carrying this gene

NCBI Reference Gene Catalog

Known alleles and reference sequences

Protein entries specific to cls

Browse AMR rules for cls

Validation StatusSupported

Overview

Mechanism: Arg218 Gln substitution
Validation Method: sequencing and MIC testing
Drug Classes: Daptomycin, Lipopeptide, DAPTOMYCIN
Organisms: Enterococcus faecium, Enterococcus faecalis, Enterococcus hirae R17, Staphylococcus aureus, Enterococcus faecium EF332, Enterococcus faecalis ATCC 29212, Rothia nasimurium, Staphylococcus simulans
Geographic Location: China, China|Xinjiang
Papers: 29
Databases: Reslit
Mutations: 32

Mutations

Protein Change	Nucleotide Change	Mechanism	Organism	Resistance To	Database	Validation Status
T33N	ACT->AAC	single resistance variant, cardiolipin synthase Cls	Staphylococcus aureus, Staphylococcus simulans	DaptomycinDAPTOMYCIN	Card DatabaseReference Gene CatalogReslit	Confirmed
R218Q	C653A	single resistance variant, cardiolipin synthase Cls	Enterococcus faecium, Enterococcus faecalis	DaptomycinDAPTOMYCIN	Card Database

Papers29

1

Genetic basis for in vivo daptomycin resistance in enterococci.

PMID 21899450 · 2011

Mutations in the genes encoding LiaF and a GdpD-family protein were necessary and sufficient for the development of resistance to daptomycin in Enterococcus faecalis. Additionally, an Arg218 Gln substitution in the Cls enzyme was found in daptomycin-resistant E. faecium isolates.

Gene Information

Gene Name: cls
Allele: cls
Encodes: cardiolipin synthetase
Source Database: Reslit
Mechanism: Arg218 Gln substitution
Confers Resistance To: Daptomycin
Organisms Tested In: • Enterococcus faecium
Validation Method: sequencing and MIC testing

2

Adaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistance.

PMID 23959318 · 2013

The study identified mutations in the liaF, liaR, yvlB, and cls genes that contribute to daptomycin resistance in Enterococcus faecalis through a defined evolutionary pathway involving the LiaFSR signaling pathway and changes in membrane composition.

Gene Information

Gene Name: cls
Allele: cls
Encodes: cardiolipin synthase
Source Database: Reslit
Mechanism: membrane synthesis
Confers Resistance To: Daptomycin
Organisms Tested In: • Enterococcus faecalis
Validation Method: whole-genome sequencing and allelic frequency measurements
Sequence Accession: SRP029594

3

Genomic insights into the pathogenicity and environmental adaptability of Enterococcus hirae R17 isolated from pork offered for retail sale.

PMID 28799224 · 2017

The study identified multiple antimicrobial resistance genes in Enterococcus hirae R17, including genes conferring resistance to beta-lactam antibiotics, lincosamides, streptogramins, pleuromutilins, polymyxins, tetracyclines, and others. Notably, the strain exhibited resistance to bacitracin, ciprofloxacin, daptomycin, erythromycin, and tetracycline.

Gene Information

Gene Name: cls
Allele: cls
Encodes: lipopeptide antibiotic, daptomycin
Source Database: Reslit
Confers Resistance To: LipopeptideDaptomycin
Organisms Tested In: • Enterococcus hirae R17
Geographic Location: China
Validation Method: genome analysis
Sequence Accession: CP015516|CP015517

4

Molecular mechanisms of thioridazine resistance in Staphylococcus aureus.

PMID 30089175 · 2018

The study identifies the cls gene as a key factor in thioridazine resistance in Staphylococcus aureus, with mutations leading to reduced susceptibility.

Gene Information

Gene Name: cls
Allele: cls
Encodes: cardiolipin synthase
Source Database: Reslit
Mechanism: mutation in the gene leads to reduced susceptibility to thioridazine
Organisms Tested In: • Staphylococcus aureus
Validation Method: deletion mutant analysis
Sequence Accession: PRJNA449536|SRP139353

5

New Mutations in cls Lead to Daptomycin Resistance in a Clinical Vancomycin- and Daptomycin-Resistant Enterococcus faecium Strain.

PMID 35801099 · 2022

The study identifies new mutations in the cls gene that confer daptomycin resistance in Enterococcus faecium EF332. Additionally, the vanA and vanM genes were found to contribute to vancomycin resistance.

Gene Information

Gene Name: cls
Allele: cls
Encodes: cardiolipin synthase
Source Database: Reslit
Confers Resistance To: Daptomycin
Organisms Tested In: • Enterococcus faecium EF332
• Enterococcus faecalis ATCC 29212
Geographic Location: China
Validation Method: molecular cloning and phenotypic screening
Sequence Accession: CP058891|CP058892|CP058893|CP058894|CP058895

6

Virulence and resistance gene analysis of Rothia nasimurium by whole gene sequencing.

PMID 40148435 · 2025

The study identified multiple AMR genes in Rothia nasimurium Y1, including vanA, vanC, vanB, vanE, vanD, vanG, vanF, vanM, vanL, vanO, vanN, mtrA, vanRA, arlR, vanRI, vanRB, vanRC, vanRD, vanRF, vanRG, CpxR, kdpE, vanRM, vanRN, baeR, adeR, vanRL, smeR, gyrA, gyrB, parC, Mfd, mfd, PBP2, PBP2x, EF-Tu, dfrE, pncA, tetB(P), tetQ, tet44, tetT, tetW, tetS, tetM, tetO, otr(A), tet36, tet32, clbC, clbB, clbA, cipA, cfrA, cfrC, sul3, ParY, murA, cls, and ileS, which confer resistance to various antibiotics such as glycopeptides, beta-lactams, fluoroquinolones, tetracyclines, sulfonamides, aminoglycosides, lincosamides, phenicols, macrolides, and others.

Gene Information

Gene Name: cls
Allele: cls
Encodes: lipopeptide synthetase
Source Database: Reslit
Confers Resistance To: Lipopeptide
Organisms Tested In: • Rothia nasimurium
Geographic Location: China|Xinjiang
Validation Method: genome sequencing
Sequence Accession: JAYWIX000000000|CP056080

7

Genomic and clinical characterization of linezolid resistance in Enterococcus species from cancer patients in China.

PMID 40775271 · 2025

The study identified the optrA gene as the primary mechanism of linezolid resistance in Enterococcus species from cancer patients in China, along with other resistance genes such as tet(M), erm(A), and erm(B).

Gene Information

Gene Name: cls
Allele: cls
Encodes: lipid II synthase
Source Database: Reslit
Organisms Tested In: • Enterococcus faecalis
Geographic Location: China
Validation Method: whole-genome sequencing
Sequence Accession: PRJNA1241515