| Accession | ARO:3003970 |
| CARD Short Name | Ddl |
| Definition | Non-van ligases that synthesize D-Ala-D-Ala, the default cell wall precursor that makes a cell vulnerable to glycopeptide antibiotics. Mutations in the ddl gene can cause the production of nonfunctional/inactivated D-Ala-D-Ala ligases, which can render bacteria glycopeptide dependent depending on the presence of vancomycin resistance clusters. |
| AMR Gene Family | Van ligase |
| Drug Class | glycopeptide antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Classification | 9 ontology terms | Show + process or component of antibiotic biology or chemistry + mechanism of antibiotic resistance + antibiotic target alteration [Resistance Mechanism] + restructuring of bacterial cell wall conferring antibiotic resistance + determinant of antibiotic resistance + protein(s) conferring antibiotic resistance via molecular bypass + antibiotic molecule + gene(s) or protein(s) associated with a glycopeptide resistance cluster + glycopeptide antibiotic [Drug Class] |
| Parent Term(s) | 2 ontology terms | Show |
| Publications | Gholizadeh Y, et al. 2001. Protein Sci. 10(4):836-44 Sequencing of the ddl gene and modeling of the mutated D-alanine:D-alanine ligase in glycopeptide-dependent strains of Enterococcus faecium. (PMID 11274474) Courvalin P. 2005. Clin Infect Dis 42(SUPPL 1): S25-S34. Vancomycin resistance in gram-positive cocci. (PMID 16323116) |
Prevalence of D-Ala-D-Ala ligase 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 |
|---|---|---|---|---|---|
| No prevalence data | |||||
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): 650
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 |
|---|---|---|
| E13G | single resistance variant | PMID:11274474 |
| +nt41:gagca | insertion mutation from nucleotide sequence | PMID:11274474 |
| G99R | single resistance variant | PMID:11274474 |
| V241D | single resistance variant | PMID:11274474 |
| -DV244-245 | deletion mutation from peptide sequence | PMID:11274474 |
| D295G | single resistance variant | PMID:11274474 |
| P313L | single resistance variant | PMID:11274474 |
| Curator | Description | Most Recent Edit |
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