| Accession | ARO:3000823 |
| CARD Short Name | ramA |
| Definition | RamA (resistance antibiotic multiple) is a positive regulator of AcrAB-TolC and leads to high level multidrug resistance in Klebsiella pneumoniae, Salmonella enterica, and Enterobacter aerugenes, increasing the expression of both the mar operon as well as AcrAB. RamA also decreases OmpF expression. |
| AMR Gene Family | General Bacterial Porin with reduced permeability to beta-lactams, resistance-nodulation-cell division (RND) antibiotic efflux pump |
| Drug Class | tetracycline antibiotic, disinfecting agents and antiseptics, penem, phenicol antibiotic, rifamycin antibiotic, penam, cephamycin, glycylcycline, cephalosporin, carbapenem, monobactam, fluoroquinolone antibiotic |
| Resistance Mechanism | reduced permeability to antibiotic, antibiotic efflux |
| Efflux Component | efflux pump complex or subunit conferring antibiotic resistance |
| Efflux Regulator | protein(s) and two-component regulatory system modulating antibiotic efflux |
| Resistomes with Sequence Variants | Enterobacter asburiaeg+wgs, Enterobacter chengduensiswgs, Enterobacter cloacaeg+wgs, Enterobacter hormaecheig+wgs, Enterobacter kobeiwgs, Enterobacter roggenkampiig+wgs, Klebsiella pneumoniaewgs |
| Classification | 32 ontology terms | Show + process or component of antibiotic biology or chemistry + antibiotic molecule + mechanism of antibiotic resistance + reduced permeability to antibiotic [Resistance Mechanism] + beta-lactam antibiotic + determinant of antibiotic resistance + cephem + protein modulating permeability to antibiotic + tetracycline antibiotic [Drug Class] + antibiotic efflux [Resistance Mechanism] + disinfecting agents and antiseptics [Drug Class] + General Bacterial Porin (GBP) + penem [Drug Class] + phenicol antibiotic [Drug Class] + efflux pump complex or subunit conferring antibiotic resistance [Efflux Component] + rifamycin antibiotic [Drug Class] + penam [Drug Class] + cephamycin [Drug Class] + glycylcycline [Drug Class] + cephalosporin [Drug Class] + carbapenem [Drug Class] + monobactam [Drug Class] + General Bacterial Porin with reduced permeability to beta-lactams [AMR Gene Family] + triclosan [Antibiotic] + cefalotin [Antibiotic] + ampicillin [Antibiotic] + chloramphenicol [Antibiotic] + rifampin [Antibiotic] + resistance-nodulation-cell division (RND) antibiotic efflux pump [AMR Gene Family] + tetracycline [Antibiotic] + tigecycline [Antibiotic] + fluoroquinolone antibiotic [Drug Class] |
| Parent Term(s) | 3 ontology terms | Show + regulates porin OmpF + regulates AcrAB-TolC + protein(s) and two-component regulatory system modulating antibiotic efflux [Efflux Regulator] |
| Publications | Chollet R, et al. 2004. Antimicrob Agents Chemother 48(7): 2518-2523. RamA is an alternate activator of the multidrug resistance cascade in Enterobacter aerogenes. (PMID 15215103) Nikaido E, et al. 2008. J Biol Chem 283(35): 24245-24253. AcrAB multidrug efflux pump regulation in Salmonella enterica serovar Typhimurium by RamA in response to environmental signals. (PMID 18577510) George AM, et al. 1995. Microbiology 141(PT 8): 1909-1920. Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. (PMID 7551053) Schneiders T, et al. 2003. Antimicrob Agents Chemother 47(9): 2831-2837. Role of AcrR and ramA in fluoroquinolone resistance in clinical Klebsiella pneumoniae isolates from Singapore. (PMID 12936981) |
Prevalence of ramA 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).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI |
|---|---|---|---|---|
| Enterobacter asburiae | 45.16% | 0% | 66.4% | 0% |
| Enterobacter chengduensis | 0% | 0% | 84% | 0% |
| Enterobacter cloacae | 58.93% | 0% | 56.23% | 0% |
| Enterobacter hormaechei | 0.36% | 0% | 0.09% | 0% |
| Enterobacter kobei | 0% | 0% | 66.81% | 0% |
| Enterobacter roggenkampii | 2.33% | 0% | 59.35% | 0% |
| Klebsiella pneumoniae | 0% | 0% | 0.01% | 0% |
Model Type: protein homolog model
Model Definition: Protein Homolog Models (PHM) detect protein sequences based on their similarity to a curated reference sequence, using curated BLASTP bitscore cut-offs. Protein Homolog Models apply to all genes that confer resistance through their presence in an organism, such as the presence of a beta-lactamase gene on a plasmid. PHMs include a reference sequence and a bitscore cut-off for detection using BLASTP. A Perfect RGI match is 100% identical to the reference protein sequence along its entire length, a Strict RGI match is not identical but the bit-score of the matched sequence is greater than the curated BLASTP bit-score cutoff, Loose RGI matches have a bit-score less than the curated BLASTP bit-score cut-off.
Bit-score Cut-off (blastP): 230