Escherichia coli AcrAB-TolC with MarR mutations conferring resistance to ciprofloxacin and tetracycline

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Ontology CARD's Antibiotic Resistance Ontology
Accession ARO:3003378
CARD Short NameEcol_MarR_MULT
DefinitionMarR is a repressor of the mar operon marRAB, thus regulating the expression of marA, the activator of multidrug efflux pump AcrAB.
AMR Gene Familyresistance-nodulation-cell division (RND) antibiotic efflux pump
Drug Classtetracycline antibiotic, penicillin beta-lactam, cephalosporin, disinfecting agents and antiseptics, phenicol antibiotic, rifamycin antibiotic, glycylcycline, fluoroquinolone antibiotic
Resistance Mechanismantibiotic efflux, antibiotic target alteration
Efflux Componentefflux pump complex or subunit conferring antibiotic resistance
Efflux Regulatorprotein(s) and two-component regulatory system modulating antibiotic efflux
Resistomes with Sequence VariantsCitrobacter amalonaticusg+wgs, Citrobacter freundiig+wgs, Citrobacter koserig+wgs, Citrobacter portucalensisg+wgs, Citrobacter werkmaniig+wgs, Citrobacter youngaeg+wgs, Cronobacter condimentig+wgs, Cronobacter dublinensisg+wgs, Cronobacter malonaticusg+wgs, Cronobacter sakazakiig+wgs, Cronobacter turicensiswgs, Cronobacter universalisg+wgs, Enterobacter asburiaeg+wgs, Enterobacter cancerogenusg+wgs, Enterobacter chengduensisg+wgs, Enterobacter cloacaeg+wgs, Enterobacter hormaecheig+wgs, Enterobacter kobeig+wgs, Enterobacter roggenkampiig+wgs, Escherichia albertiig+wgs, Escherichia colig+p+wgs, Escherichia fergusoniig+wgs, Escherichia marmotaeg+wgs, Klebsiella aerogenesg+wgs, Klebsiella huaxiensisg+wgs, Klebsiella michiganensisg+wgs, Klebsiella oxytocag+wgs, Klebsiella pneumoniaeg+p+wgs, Klebsiella quasipneumoniaeg+wgs, Kosakonia arachidisg+wgs, Leclercia adecarboxylatag+wgs, Raoultella planticolag+wgs, Salmonella bongorig+wgs, Salmonella entericag+wgs, Shigella boydiig+wgs, Shigella dysenteriaeg+wgs, Shigella flexnerig+wgs, Shigella sonneig+wgs
Classification31 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ confers_resistance_to_antibiotic ciprofloxacin [Antibiotic]
+ confers_resistance_to_antibiotic tetracycline [Antibiotic]
+ marR
Publications

Alekshun MN and Levy SB. 1997. Antimicrob Agents Chemother 41(10): 2067-2075. Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. (PMID 9333027)

Randall LP and Woodward MJ. 2002. Res Vet Sci 72(2): 87-93. The multiple antibiotic resistance (mar) locus and its significance. (PMID 12027588)

Oethinger M, et al. 1998. Antimicrob. Agents Chemother. 42(8):2089-94 Overexpression of the marA or soxS regulatory gene in clinical topoisomerase mutants of Escherichia coli. (PMID 9687412)

Maneewannakul K, et al. 1996. Antimicrob. Agents Chemother. 40(7):1695-8 Identification for mar mutants among quinolone-resistant clinical isolates of Escherichia coli. (PMID 8807064)

Okusu H, et al. 1996. J Bacteriol 178(1): 306-308. AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants. (PMID 8550435)

Alekshun MN, et al. 2000. Mol Microbiol 35(6):1394-404 Mutational analysis of MarR, the negative regulator of marRAB expression in Escherichia coli, suggests the presence of two regions required for DNA binding. (PMID 10760140)

Webber MA, et al. 2001. Antimicrob. Agents Chemother. 45(5):1550-2 Absence of mutations in marRAB or soxRS in acrB-overexpressing fluoroquinolone-resistant clinical and veterinary isolates of Escherichia coli. (PMID 11302826)
Resistomes

Prevalence of Escherichia coli AcrAB-TolC with MarR mutations conferring resistance to ciprofloxacin and tetracycline 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).

Prevalence: protein overexpression model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GIGRDI-AMR2
Citrobacter amalonaticus100%0%100%0%0%
Citrobacter freundii100%0%99.03%0%0%
Citrobacter koseri100%0%100%0%0%
Citrobacter portucalensis100%0%100%0%0%
Citrobacter werkmanii100%0%100%0%0%
Citrobacter youngae100%0%100%0%0%
Cronobacter condimenti100%0%100%0%0%
Cronobacter dublinensis100%0%100%0%0%
Cronobacter malonaticus100%0%98.18%0%0%
Cronobacter sakazakii100%0%99.1%0%0%
Cronobacter turicensis0%0%100%0%0%
Cronobacter universalis100%0%66.67%0%0%
Enterobacter asburiae100%0%98.42%0%0%
Enterobacter cancerogenus100%0%100%0%0%
Enterobacter chengduensis100%0%100%0%0%
Enterobacter cloacae98.21%0%99.04%0%0%
Enterobacter hormaechei98.56%0%99.18%0%0%
Enterobacter kobei100%0%99.13%0%0%
Enterobacter roggenkampii100%0%100%0%0%
Escherichia albertii95.71%0%97.42%0%0%
Escherichia coli67.65%0.06%98.85%0%99.73%
Escherichia fergusonii100%0%100%0%0%
Escherichia marmotae100%0%97.92%0%0%
Klebsiella aerogenes100%0%99.72%0%0%
Klebsiella huaxiensis100%0%100%0%0%
Klebsiella michiganensis100%0%99.47%0%0%
Klebsiella oxytoca100%0%99.16%0%0%
Klebsiella pneumoniae99.11%0.01%99.07%0%0%
Klebsiella quasipneumoniae100%0%99.61%0%0%
Kosakonia arachidis100%0%100%0%0%
Leclercia adecarboxylata100%0%100%0%0%
Raoultella planticola100%0%100%0%0%
Salmonella bongori100%0%100%0%0%
Salmonella enterica95.39%0%99.16%0%0%
Shigella boydii93.33%0%95.56%0%0%
Shigella dysenteriae100%0%90%0%0%
Shigella flexneri100%0%98.29%0%0%
Shigella sonnei100%0%97.88%0%0%
Show Perfect Only


Detection Models

Model Type: protein overexpression model

Model Definition: Protein Overexpression Models (POM) are similar to Protein Variant Models (PVM) in that they include a protein reference sequence, a curated BLASTP bitscore cut-off, and mapped resistance variants. Whereas PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, reporting only those with curated mutations conferring AMR, POMs are restricted to regulatory proteins and report both wild-type sequences and/or sequences with mutations leading to overexpression of efflux complexes. The former lead to efflux of antibiotics at basal levels, while the latter can confer clinical resistance. POMs include a protein reference sequence (often from 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 Perfect RGI match is 100% identical to the wild-type reference protein sequence along its entire length, a Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value may or may not contain 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 may or may not contain at least one curated mutation from amongst the mapped resistance variants.

Bit-score Cut-off (blastP): 210

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).

MutationMutation typePubMed
S3Nsingle resistance variantPMID:8807064
E31Ternonsense mutationPMID:9687412
V45Esingle resistance variantPMID:10760140
I49Ssingle resistance variantPMID:9687412
R58Lsingle resistance variantPMID:8550435
A70Tsingle resistance variantPMID:10760140
R73Csingle resistance variantPMID:10760140
R73Ssingle resistance variantPMID:10760140
R77Csingle resistance variantPMID:10760140
R77Lsingle resistance variantPMID:10760140
L78Msingle resistance variantPMID:9687412
R94Hsingle resistance variantPMID:9687412
R94Ssingle resistance variantPMID:9687412
V96Esingle resistance variantPMID:8807064
G103Ssingle resistance variantPMID:8807064
Y137Hsingle resistance variantPMID:11302826

>gb|AAC74603.2|+|Escherichia coli AcrAB-TolC with MarR mutations conferring resistance to ciprofloxacin and tetracycline [Escherichia coli str. K-12 substr. MG1655]
MKSTSDLFNEIIPLGRLIHMVNQKKDRLLNEYLSPLDITAAQFKVLCSIRCAACITPVEL
KKVLSVDLGALTRMLDRLVCKGWVERLPNPNDKRGVLVKLTTGGAAICEQCHQLVGQDLH
QELTKNLTADEVATLEYLLKKVLP


>gb|U00096.1|+|1619120-1619554|Escherichia coli AcrAB-TolC with MarR mutations conferring resistance to ciprofloxacin and tetracycline [Escherichia coli str. K-12 substr. MG1655]
GTGAAAAGTACCAGCGATCTGTTCAATGAAATTATTCCATTGGGTCGCTTAATCCATATGGTTAATCAGAAGAAAGATCGCCTGCTTAAC
GAGTATCTGTCTCCGCTGGATATTACCGCGGCACAGTTTAAGGTGCTCTGCTCTATCCGCTGCGCGGCGTGTATTACTCCGGTTGAACTG
AAAAAGGTATTGTCGGTCGACCTGGGAGCACTGACCCGTATGCTGGATCGCCTGGTCTGTAAAGGCTGGGTGGAAAGGTTGCCGAACCCG
AATGACAAGCGCGGCGTACTGGTAAAACTTACCACCGGCGGCGCGGCAATATGTGAACAATGCCATCAATTAGTTGGCCAGGACCTGCAC
CAAGAATTAACAAAAAACCTGACGGCGGACGAAGTGGCAACACTTGAGTATTTGCTTAAGAAAGTCCTGCCGTAA

Curator Acknowledgements
Curator Description Most Recent Edit