| Accession | ARO:3003092 |
| Synonym(s) | cls1 cls2 |
| CARD Short Name | Efac_cls_DAP |
| Definition | cls or cardiolipin synthetase is an inner membrane protein that is involved in membrane synthesis. Specific mutations in Enterococcus can confer resistance to daptomycin. |
| AMR Gene Family | daptomycin resistant cls |
| Drug Class | peptide antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Enterococcus faeciumg+wgs |
| Classification | 10 ontology terms | Show + process or component of antibiotic biology or chemistry + antibiotic molecule + mechanism of antibiotic resistance + peptide antibiotic [Drug Class] + antibiotic target alteration [Resistance Mechanism] + mutation conferring antibiotic resistance + lipopeptide antibiotic + determinant of antibiotic resistance + daptomycin [Antibiotic] + antibiotic resistant gene variant or mutant |
| 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 | Arias CA, et al. 2011. N Engl J Med 365(10): 892-900. Genetic basis for in vivo daptomycin resistance in enterococci. (PMID 21899450) Kelesidis T, et al. 2013. J Antimicrob Chemother 68(8): 1926-1928. Evolution of high-level daptomycin resistance in Enterococcus faecium during daptomycin therapy is associated with limited mutations in the bacterial genome. (PMID 23580562) 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) Humphries RM, et al. 2012. Antimicrob Agents Chemother 56(11): 6051-6053. Genotypic and phenotypic evaluation of the evolution of high-level daptomycin nonsusceptibility in vancomycin-resistant Enterococcus faecium. (PMID 22948885) Lellek H, et al. 2015. Int. J. Med. Microbiol. 305(8):902-9 Emergence of daptomycin non-susceptibility in colonizing vancomycin-resistant Enterococcus faecium isolates during daptomycin therapy. (PMID 26454536) |
Prevalence of Enterococcus faecium cls conferring resistance to daptomycin among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 414 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).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI | GRDI-AMR2 |
|---|---|---|---|---|---|
| Enterococcus faecium | 2.55% | 0% | 0.78% | 0% | 0% |
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
PubMed: mutation data hand curated from the scientific literature, evaluated as conferring resistance (R). CRyPTIC: mutation data acquired from the CRyPTIC catalog, evaluated as resistant (R), susceptible (S), or undetermined (U). ReSeqTB: mutation data acquired from the ReSeqTB catalog, evaluated as conferring resistance (Minimal, Moderate, High), not conferring resistance (None), or Indeterminate. WHO: mutation data acquired from the WHO 2023 catalog, evaluated as resistant (R), susceptible (S), or undetermined (U).| Mutation | Mutation type | PubMed |
|---|---|---|
| N13T | single resistance variant | PMID:23580562 |
| N13I | single resistance variant | PMID:21899450 |
| A20D | single resistance variant | PMID:26454536 |
| D27N | single resistance variant | PMID:26454536 |
| K59T | single resistance variant | PMID:23580562 |
| +MPL110-112 | insertion mutation from peptide sequence | PMID:21899450 |
| G177T | single resistance variant | PMID:23580562 |
| H215R | single resistance variant | PMID:23114777 |
| R267H | single resistance variant | PMID:26454536 |
| Curator | Description | Most Recent Edit |
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