Accession ARO:3000237
CARD Short NameTolC
DefinitionTolC 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 Familyresistance-nodulation-cell division (RND) antibiotic efflux pump, major facilitator superfamily (MFS) antibiotic efflux pump, ATP-binding cassette (ABC) antibiotic efflux pump
Drug Classpeptide antibiotic, aminoglycoside antibiotic, tetracycline antibiotic, aminocoumarin antibiotic, macrolide antibiotic, penem, fluoroquinolone antibiotic, cephalosporin, penam, glycylcycline, carbapenem, rifamycin antibiotic, disinfecting agents and antiseptics, phenicol antibiotic, cephamycin
Resistance Mechanismantibiotic efflux
Efflux Componentefflux pump complex or subunit conferring antibiotic resistance
Resistomes with Perfect MatchesEscherichia colig+p, Shigella boydiig, Shigella dysenteriaeg, Shigella flexnerig, Shigella sonneig
Resistomes with Sequence VariantsEscherichia albertiig, Escherichia colig+p, Escherichia fergusoniig, Escherichia marmotaeg, Shigella boydiig, Shigella dysenteriaeg, Shigella flexnerig, Shigella sonneig
Classification60 ontology terms | Show
+ process or component of antibiotic biology or chemistry
+ antibiotic molecule
+ mechanism of antibiotic resistance
+ peptide antibiotic [Drug Class]
+ beta-lactam antibiotic
+ lipopeptide antibiotic
+ antibiotic efflux [Resistance Mechanism]
+ determinant of antibiotic resistance
+ antibiotic mixture
+ polymyxin antibiotic
+ cephem
+ aminoglycoside antibiotic [Drug Class]
+ efflux pump complex or subunit conferring antibiotic resistance [Efflux Component]
+ tetracycline antibiotic [Drug Class]
+ polymyxin B [Antibiotic]
+ aminocoumarin antibiotic [Drug Class]
+ macrolide antibiotic [Drug Class]
+ penem [Drug Class]
+ fluoroquinolone antibiotic [Drug Class]
+ cephalosporin [Drug Class]
+ penam [Drug Class]
+ glycylcycline [Drug Class]
+ carbapenem [Drug Class]
+ resistance-nodulation-cell division (RND) antibiotic efflux pump [AMR Gene Family]
+ rifamycin antibiotic [Drug Class]
+ disinfecting agents and antiseptics [Drug Class]
+ gentamicin [Antibiotic]
+ phenicol antibiotic [Drug Class]
+ cephamycin [Drug Class]
+ major facilitator superfamily (MFS) antibiotic efflux pump [AMR Gene Family]
+ gentamicin C [Antibiotic]
+ ceftazidime [Antibiotic]
+ AcrEF-TolC
+ tetracycline [Antibiotic]
+ polymyxin B1 [Antibiotic]
+ polymyxin B2 [Antibiotic]
+ polymyxin B4 [Antibiotic]
+ ATP-binding cassette (ABC) antibiotic efflux pump [AMR Gene Family]
+ polymyxin B3 [Antibiotic]
+ erythromycin [Antibiotic]
+ azithromycin [Antibiotic]
+ streptomycin [Antibiotic]
+ nalidixic acid [Antibiotic]
+ piperacillin [Antibiotic]
+ imipenem [Antibiotic]
+ triclosan [Antibiotic]
+ chloramphenicol [Antibiotic]
+ ticarcillin [Antibiotic]
+ ertapenem [Antibiotic]
+ tobramycin [Antibiotic]
+ ciprofloxacin [Antibiotic]
+ spectinomycin [Antibiotic]
+ norfloxacin [Antibiotic]
+ cloxacillin [Antibiotic]
+ cefalotin [Antibiotic]
+ ampicillin [Antibiotic]
+ novobiocin [Antibiotic]
+ oxacillin [Antibiotic]
+ rifampin [Antibiotic]
+ tigecycline [Antibiotic]
Parent Term(s)10 ontology terms | Show
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)

Resistomes

Prevalence of TolC among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 381 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 homolog model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Escherichia albertii7.14%0%0%0%
Escherichia coli67.77%0.04%0%0%
Escherichia fergusonii88.52%0%0%0%
Escherichia marmotae100%0%0%0%
Shigella boydii100%0%0%0%
Shigella dysenteriae100%0%0%0%
Shigella flexneri98%0%0%0%
Shigella sonnei100%0%0%0%
Show Perfect Only


Detection Models

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


>gb|ACN32294.1|+|TolC [Escherichia coli]
MQMKKLLPILIGLSLSGFSSLSQAENLMQVYQQARLSNPELRKSAADRDAAFEKINEARSPLLPQLGLGADYTYSNGYRDANGINSNATS
ASLQLTQSIFDMSKWRALTLQEKAAGIQDVTYQTDQQTLILNTATAYFNVLNAIDVLSYTQAQKEAIYRQLDQTTQRFNVGLVAITDVQN
ARAQYDTVLANEVTARNNLDNAVEQLRQITGNYYPELAALNVENFKTDKPQPVNALLKEAEKRNLSLLQARLSQDLAREQIRQAQDGHLP
TLDLTASTGISDTSYSGSKTRGAAGTQYDDSNMGQNKVGLSFSLPIYQGGMVNSQVKQAQYNFVGASEQLESAHRSVVQTVRSSFNNINA
SISSINAYKQAVVSAQSSLDAMEAGYSVGTRTIVDVLDATTTLYNAKQELANARYNYLINQLNIKSALGTLNEQDLLALNNALSKPVSTN
PENVAPQTPEQNAIADGYAPDSPAPVVQQTSARTTTSNGHNPFRN


>gb|FJ768952.1|+|1-1488|TolC [Escherichia coli]
ATGCAAATGAAGAAATTGCTCCCCATTCTTATCGGCCTGAGCCTTTCTGGGTTCAGTTCGTTGAGCCAGGCCGAGAACCTGATGCAAGTT
TATCAGCAAGCACGCCTTAGTAACCCGGAATTGCGTAAGTCTGCCGCCGATCGTGATGCTGCCTTTGAAAAAATTAATGAAGCGCGCAGT
CCATTACTGCCACAGCTAGGTTTAGGTGCAGATTACACCTATAGCAACGGCTACCGCGACGCGAACGGCATCAACTCTAACGCGACCAGT
GCGTCCTTGCAGTTAACTCAATCCATTTTTGATATGTCGAAATGGCGTGCGTTAACGCTGCAGGAAAAAGCAGCAGGGATTCAGGACGTC
ACGTATCAGACCGATCAGCAAACCTTGATCCTCAACACCGCGACCGCTTATTTCAACGTGTTGAATGCTATTGACGTTCTTTCCTATACA
CAGGCACAAAAAGAAGCGATCTACCGTCAATTAGATCAAACCACCCAACGTTTTAACGTGGGCCTGGTAGCGATCACCGACGTGCAGAAC
GCCCGCGCACAGTACGATACCGTGCTGGCGAACGAAGTGACCGCACGTAATAACCTTGATAACGCGGTAGAGCAGCTGCGCCAGATCACC
GGTAACTACTATCCGGAACTGGCTGCGCTGAATGTCGAAAACTTTAAAACCGACAAACCACAGCCGGTTAACGCGCTGCTGAAAGAAGCC
GAAAAACGCAACCTGTCGCTGTTACAGGCACGCTTGAGCCAGGACCTGGCGCGCGAGCAAATTCGCCAGGCGCAGGATGGTCACTTACCG
ACTCTGGATTTAACGGCTTCTACCGGGATTTCTGACACCTCTTATAGCGGTTCGAAAACCCGTGGTGCCGCTGGTACCCAGTATGACGAT
AGCAATATGGGCCAGAACAAAGTTGGCCTGAGCTTCTCGCTGCCGATTTATCAGGGCGGAATGGTTAACTCGCAGGTGAAACAGGCACAG
TACAACTTTGTCGGTGCCAGCGAGCAACTGGAAAGTGCCCATCGTAGCGTCGTGCAGACCGTGCGTTCCTCCTTCAACAACATTAATGCA
TCTATCAGTAGCATTAACGCCTACAAACAAGCCGTAGTTTCCGCTCAAAGCTCATTAGACGCGATGGAAGCGGGCTACTCGGTCGGTACG
CGTACCATTGTTGATGTGTTGGATGCGACCACCACGTTGTACAACGCCAAGCAAGAGCTGGCGAATGCGCGTTATAACTACCTGATTAAT
CAGCTGAATATTAAGTCAGCTCTGGGTACGTTGAACGAGCAGGATCTGCTGGCACTGAACAATGCGCTGAGCAAACCGGTTTCCACTAAT
CCGGAAAACGTTGCACCGCAAACGCCGGAACAGAATGCTATTGCTGATGGTTATGCGCCTGATAGCCCGGCACCAGTCGTTCAGCAAACA
TCCGCACGCACTACCACCAGTAACGGTCATAACCCTTTCCGTAACTGA