Accession ARO:3000237
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, tetracycline antibiotic, penam, rifamycin antibiotic, phenicol antibiotic, fluoroquinolone antibiotic, aminoglycoside antibiotic, penem, glycylcycline, carbapenem, macrolide antibiotic, aminocoumarin antibiotic, cephalosporin, cephamycin, triclosan
Resistance Mechanismantibiotic efflux
Efflux Componentefflux pump complex or subunit conferring antibiotic resistance
Resistomes with Perfect MatchesEscherichia colig+p+wgs, Klebsiella oxytocawgs, Salmonella entericawgs, Shigella dysenteriaeg+wgs, Shigella flexnerig+wgs, Shigella sonneig+wgs
Resistomes with Sequence VariantsAcinetobacter baumanniiwgs, Acinetobacter nosocomialiswgs, Enterobacter hormaecheiwgs, Enterobacter kobeiwgs, Enterococcus faeciumwgs, Escherichia colig+p+wgs, Klebsiella aerogeneswgs, Klebsiella oxytocawgs, Klebsiella pneumoniaewgs, Morganella morganiiwgs, Salmonella entericawgs, Serratia marcescenswgs, Shigella dysenteriaeg+wgs, Shigella flexnerig+wgs, Shigella sonneig+wgs
Classification59 ontology terms | Show
+ process or component of antibiotic biology or chemistry
+ antibiotic molecule
+ peptide antibiotic [Drug Class]
+ mechanism of antibiotic resistance
+ determinant of antibiotic resistance
+ beta-lactam antibiotic
+ lipopeptide antibiotic
+ antibiotic efflux [Resistance Mechanism]
+ polymyxin antibiotic
+ tetracycline antibiotic [Drug Class]
+ antibiotic mixture
+ cephem
+ efflux pump complex or subunit conferring antibiotic resistance [Efflux Component]
+ resistance-nodulation-cell division (RND) antibiotic efflux pump [AMR Gene Family]
+ penam [Drug Class]
+ rifamycin antibiotic [Drug Class]
+ phenicol antibiotic [Drug Class]
+ fluoroquinolone antibiotic [Drug Class]
+ polymyxin B
+ aminoglycoside antibiotic [Drug Class]
+ penem [Drug Class]
+ glycylcycline [Drug Class]
+ carbapenem [Drug Class]
+ macrolide antibiotic [Drug Class]
+ antibiotic without defined classification
+ aminocoumarin antibiotic [Drug Class]
+ cephalosporin [Drug Class]
+ cephamycin [Drug Class]
+ major facilitator superfamily (MFS) antibiotic efflux pump [AMR Gene Family]
+ spectinomycin [Antibiotic]
+ gentamicin C [Antibiotic]
+ erythromycin [Antibiotic]
+ norfloxacin [Antibiotic]
+ cloxacillin [Antibiotic]
+ piperacillin [Antibiotic]
+ ceftazidime [Antibiotic]
+ polymyxin B3 [Antibiotic]
+ polymyxin B1 [Antibiotic]
+ polymyxin B2 [Antibiotic]
+ AcrEF-TolC
+ polymyxin B4 [Antibiotic]
+ ATP-binding cassette (ABC) antibiotic efflux pump [AMR Gene Family]
+ nalidixic acid [Antibiotic]
+ azithromycin [Antibiotic]
+ ticarcillin [Antibiotic]
+ oxacillin [Antibiotic]
+ streptomycin [Antibiotic]
+ triclosan [Drug Class]
+ chloramphenicol [Antibiotic]
+ tetracycline [Antibiotic]
+ ertapenem [Antibiotic]
+ imipenem [Antibiotic]
+ ciprofloxacin [Antibiotic]
+ cefalotin [Antibiotic]
+ novobiocin [Antibiotic]
+ ampicillin [Antibiotic]
+ rifampin [Antibiotic]
+ tigecycline [Antibiotic]
+ tobramycin [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 for 88 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, 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 WGS
Acinetobacter baumannii0%0%0.05%
Acinetobacter nosocomialis0%0%1.1%
Citrobacter freundii0%0%0%
Enterobacter hormaechei0%0%0.12%
Enterobacter kobei0%0%1.45%
Enterococcus faecium0%0%0.06%
Escherichia coli51.25%0.02%96.97%
Klebsiella aerogenes0%0%0.47%
Klebsiella oxytoca0%0%0.39%
Klebsiella pneumoniae0%0%0.33%
Morganella morganii0%0%1.79%
Proteus mirabilis0%0%0%
Pseudomonas putida0%0%0%
Salmonella enterica0%0%0.13%
Serratia marcescens0%0%0.18%
Shigella dysenteriae100%0%100%
Shigella flexneri100%0%99.67%
Shigella sonnei100%0%100%
Show Perfect Only


Detection Models

Model Type: protein homolog model

Model Definition: The protein homolog model is an AMR detection model. Protein homolog models detect a protein sequence based on its similarity to a curated reference sequence. A protein homolog model has only one parameter: a curated BLASTP bitscore cutoff for determining the strength of a match. Protein homolog model matches to reference sequences are categorized on three criteria: perfect, strict and loose. A perfect match is 100% identical to the reference sequence along its entire length; a strict match is not identical but the bitscore of the matched sequence is greater than the curated BLASTP bitscore cutoff. Loose matches are other sequences with a match bitscore less than the curated BLASTP bitscore.

Bit-score Cut-off (blastP): 900


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


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