| Accession | ARO:3000237 |
| CARD Short Name | TolC |
| Definition | TolC is a protein subunit of many multidrug efflux complexes in Gram negative bacteria. It is an outer membrane efflux protein and is constitutively open. Regulation of efflux activity is often at its periplasmic entrance by other components of the efflux complex. |
| AMR Gene Family | resistance-nodulation-cell division (RND) antibiotic efflux pump, major facilitator superfamily (MFS) antibiotic efflux pump, ATP-binding cassette (ABC) antibiotic efflux pump |
| Drug Class | peptide antibiotic, aminoglycoside antibiotic, tetracycline antibiotic, macrolide antibiotic, fluoroquinolone antibiotic, penam, carbapenem, penem, aminocoumarin antibiotic, phenicol antibiotic, cephalosporin, disinfecting agents and antiseptics, glycylcycline, rifamycin antibiotic, cephamycin |
| Resistance Mechanism | antibiotic efflux |
| Efflux Component | efflux pump complex or subunit conferring antibiotic resistance |
| Resistomes with Perfect Matches | Escherichia colig+p+wgs, Shigella boydiig+wgs, Shigella dysenteriaeg+wgs, Shigella flexnerig+wgs, Shigella sonneig+wgs |
| Resistomes with Sequence Variants | Escherichia albertiig+wgs, Escherichia colig+p+wgs, Escherichia fergusoniig+wgs, Escherichia marmotaeg+wgs, Shigella boydiig+wgs, Shigella dysenteriaeg+wgs, Shigella flexnerig+wgs, Shigella sonneig+wgs |
| Classification | 60 ontology terms | Show + process or component of antibiotic biology or chemistry + antibiotic molecule + peptide antibiotic [Drug Class] + mechanism of antibiotic resistance + lipopeptide antibiotic + determinant of antibiotic resistance + beta-lactam antibiotic + antibiotic efflux [Resistance Mechanism] + antibiotic mixture + cephem + polymyxin antibiotic + aminoglycoside antibiotic [Drug Class] + tetracycline antibiotic [Drug Class] + efflux pump complex or subunit conferring antibiotic resistance [Efflux Component] + macrolide antibiotic [Drug Class] + fluoroquinolone antibiotic [Drug Class] + polymyxin B [Antibiotic] + penam [Drug Class] + gentamicin [Antibiotic] + resistance-nodulation-cell division (RND) antibiotic efflux pump [AMR Gene Family] + carbapenem [Drug Class] + penem [Drug Class] + aminocoumarin antibiotic [Drug Class] + phenicol antibiotic [Drug Class] + cephalosporin [Drug Class] + disinfecting agents and antiseptics [Drug Class] + glycylcycline [Drug Class] + rifamycin antibiotic [Drug Class] + cephamycin [Drug Class] + polymyxin B1 [Antibiotic] + chloramphenicol [Antibiotic] + polymyxin B2 [Antibiotic] + polymyxin B4 [Antibiotic] + nalidixic acid [Antibiotic] + erythromycin [Antibiotic] + streptomycin [Antibiotic] + gentamicin C [Antibiotic] + piperacillin [Antibiotic] + imipenem [Antibiotic] + major facilitator superfamily (MFS) antibiotic efflux pump [AMR Gene Family] + ceftazidime [Antibiotic] + norfloxacin [Antibiotic] + cloxacillin [Antibiotic] + triclosan [Antibiotic] + polymyxin B3 [Antibiotic] + ticarcillin [Antibiotic] + AcrEF-TolC + ertapenem [Antibiotic] + tetracycline [Antibiotic] + azithromycin [Antibiotic] + tobramycin [Antibiotic] + spectinomycin [Antibiotic] + ciprofloxacin [Antibiotic] + cefalotin [Antibiotic] + rifampin [Antibiotic] + ATP-binding cassette (ABC) antibiotic efflux pump [AMR Gene Family] + ampicillin [Antibiotic] + novobiocin [Antibiotic] + oxacillin [Antibiotic] + tigecycline [Antibiotic] |
| Parent Term(s) | 10 ontology terms | Show + part_of AcrAB-TolC + part_of MacAB-TolC + part_of EmrAB-TolC + part_of EmrKY-TolC + part_of AcrEF-TolC + part_of MdtABC-TolC + part_of MdtEF-TolC + subunit of efflux pump conferring antibiotic resistance + part_of Klebsiella pneumoniae KpnGH-TolC + part_of AcrEF-TolC confers resistance to ciprofloxacin |
| Publications | Koronakis V. 2003. FEBS Lett 555(1): 66-71. TolC--the bacterial exit duct for proteins and drugs. (PMID 14630321) Koronakis V, et al. 2000. Nature 405(6789): 914-919. Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. (PMID 10879525) Sharff A, et al. 2001. Eur J Biochem 268(19): 5011-5026. The role of the TolC family in protein transport and multidrug efflux. From stereochemical certainty to mechanistic hypothesis. (PMID 11589692) Andersen C, et al. 2002. Proc Natl Acad Sci U S A 99(17): 11103-11108. Transition to the open state of the TolC periplasmic tunnel entrance. (PMID 12163644) Nishino K, et al. 2005. Mol Microbiol 59(1): 126-141. Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. (PMID 16359323) |
Prevalence of TolC 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 |
|---|---|---|---|---|
| Escherichia albertii | 7.14% | 0% | 5.81% | 0% |
| Escherichia coli | 67.77% | 0.04% | 61.61% | 0% |
| Escherichia fergusonii | 88.52% | 0% | 43.48% | 0% |
| Escherichia marmotae | 100% | 0% | 70.83% | 0% |
| Shigella boydii | 100% | 0% | 97.78% | 0% |
| Shigella dysenteriae | 100% | 0% | 100% | 0% |
| Shigella flexneri | 98% | 0% | 81.37% | 0% |
| Shigella sonnei | 100% | 0% | 95.69% | 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): 900
