Enterococcus faecalis cls with mutation conferring resistance to daptomycin

Accession ARO:3003760
CARD Short NameEfae_cls_DAP
DefinitionCardiolipin synthase (cls) is an inner membrane protein involved in membrane synthesis and phosopholipid metabolism, with mutations to the gene being capable of conferring daptomycin resistance.
AMR Gene Familydaptomycin resistant cls
Drug Classpeptide antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsEnterococcus faecaliswgs
Classification10 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ confers_resistance_to_antibiotic daptomycin [Antibiotic]
+ daptomycin resistant cls [AMR Gene Family]
+ derives_from Daptomycin sensitive cardiolipin synthetase
Publications

Werth BJ, et al. 2014. Antimicrob. Agents Chemother. 58(9):5253-61 Defining daptomycin resistance prevention exposures in vancomycin-resistant Enterococcus faecium and E. faecalis. (PMID 24957825)

Davlieva M, et al. 2012. Antimicrob Agents Chemother 57(1): 289-296. Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci. (PMID 23114777)

Miller C, et al. 2013. Antimicrob Agents Chemother 57(11): 5373-5383. Adaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistance. (PMID 23959318)

Resistomes

Prevalence of Enterococcus faecalis cls with mutation conferring resistance to daptomycin among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 413 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Enterococcus faecalis0%0%0.04%0%
Show Perfect Only


Detection Models

Model Type: protein variant model

Model Definition: Protein Variant Models (PVM) perform a similar search as Protein Homolog Models (PHM), i.e. detect protein sequences based on their similarity to a curated reference sequence, but secondarily screen query sequences for curated sets of mutations to differentiate them from antibiotic susceptible wild-type alleles. PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, e.g. a mutated gyrase resistant to aminocoumarin antibiotics. PVMs include a protein reference sequence (often from antibiotic susceptible wild-type alleles), a curated bit-score cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of single point mutations, insertions, or deletions curated from the scientific literature. A Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value and contains at least one curated mutation from amongst the mapped resistance variants, while a Loose RGI match has a bit-score less than the curated BLASTP bit-score cut-off but still contains at least one curated mutation from amongst the mapped resistance variants.

Bit-score Cut-off (blastP): 900

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 24957825R218Q R267H
PMID: 23114777H215R
PMID: 23959318+AII14-16 -K61 -NFQ74-76

>gb|AEA93051.1|+|Enterococcus faecalis cls with mutation conferring resistance to daptomycin [Enterococcus faecalis OG1RF]
MILSVLTVIYFINAIIAGITILLKPRDVAAIWAWLLVLIALPVFGFFLYLFFGRGLTDKK
KFYLQQSDLRELENFQNFQEESFELYSQKMPTEEQQQFTDFFSSLNRMPLTKKNDVEIFT
DGTEKFNALMADIKKAQHSIHIEYYAFVTDHIGTKILNLLEEKAAEGVEVRLLYDAFGSK
GTKVHHLNELKKNGGFVQTFITSQKALLKFRLNYHDHRKIVVIDGKVGYIGGFNVADQYA
GTTKKFGYWRDTHLRIQGPATSLLQMRFLMDWNVSSPEKNRVAYQLDYFFKLEALVPEAN
TSIQMIASGPNSDREQIKLAFIKLITSAKKRVWIQTPYLVPDDSVLAALKVAAASGVDVK
IMIPDKPDHPFIYRATQYYGRLLMKENIEILIYNGGFLHAKTMIMDDEVCTVGSANQDIR
SYKLNFEANAVLYDKKIIDQLEAIFLEDRKKCTTMTPEVVRDMSKWLIFKQQISRLFSPI
L



>gb|CP002621.1|+|376486-377931|Enterococcus faecalis cls with mutation conferring resistance to daptomycin [Enterococcus faecalis OG1RF]
TTGATTCTTAGCGTCTTAACAGTTATTTATTTTATTAATGCAATTATTGCGGGAATTACCATTTTGTTAAAACCTCGAGATGTAGCAGCA
ATTTGGGCATGGCTACTCGTACTGATTGCTCTACCCGTTTTTGGTTTTTTCTTATATTTATTCTTTGGTCGCGGTTTAACCGACAAAAAG
AAATTTTATTTGCAACAAAGTGATTTGCGGGAATTAGAGAATTTTCAGAATTTCCAAGAAGAAAGTTTTGAACTTTATAGTCAAAAGATG
CCGACGGAGGAGCAACAACAGTTTACAGACTTTTTTTCCTCGTTAAATAGGATGCCTCTGACTAAGAAAAATGATGTTGAAATTTTTACG
GATGGTACGGAAAAATTCAATGCGTTGATGGCGGATATAAAAAAAGCTCAGCACTCCATTCATATTGAATATTATGCCTTTGTAACGGAT
CATATCGGTACCAAAATTTTGAACTTATTAGAAGAAAAGGCGGCTGAAGGGGTTGAAGTGCGGTTGCTTTACGATGCCTTTGGCTCAAAG
GGCACCAAGGTTCATCATTTGAATGAATTGAAAAAAAACGGTGGTTTTGTCCAAACGTTTATTACTTCTCAAAAAGCACTTTTGAAGTTT
CGTTTGAATTATCATGATCACCGGAAAATTGTTGTTATTGACGGAAAAGTAGGCTACATTGGCGGCTTTAATGTTGCCGATCAATATGCC
GGAACGACTAAAAAGTTTGGCTATTGGCGGGATACACATTTACGGATTCAAGGGCCAGCAACCTCATTACTGCAAATGCGTTTTTTAATG
GATTGGAACGTCTCTTCCCCCGAGAAAAATCGTGTGGCGTATCAATTGGATTATTTCTTTAAACTTGAAGCATTGGTGCCAGAGGCAAAT
ACATCCATTCAGATGATTGCCAGTGGTCCTAACAGTGACCGTGAACAAATTAAATTGGCCTTTATTAAATTGATTACTTCTGCCAAGAAA
AGAGTCTGGATTCAAACGCCGTATTTAGTTCCTGATGATAGTGTCTTGGCTGCTTTAAAGGTTGCTGCGGCTTCAGGAGTAGATGTTAAA
ATTATGATTCCAGATAAGCCCGACCATCCGTTTATTTATCGAGCAACACAGTATTACGGCCGCTTATTGATGAAAGAAAATATTGAAATT
TTAATTTATAACGGTGGTTTCTTACATGCGAAAACAATGATTATGGATGATGAAGTCTGCACAGTTGGTTCAGCCAATCAAGATATCCGA
AGTTACAAATTAAACTTTGAAGCAAATGCTGTGTTATATGATAAAAAAATCATTGATCAATTAGAAGCAATTTTCTTAGAAGATCGAAAA
AAATGTACAACAATGACTCCAGAAGTTGTTCGTGACATGTCAAAATGGTTGATTTTTAAACAACAAATTTCACGATTATTTTCACCAATT
CTTTAA