ArticlePloS one2017
The Vibrio cholerae var regulon encodes a metallo-β-lactamase and an antibiotic efflux pump, which are regulated by VarR, a LysR-type transcription factor.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
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- Epidemiological and genetic charateristics of Vibrio vulnificus from diverse sources in China during 2012-2023.Communications biology · 2025Article
- LysR-type transcriptional regulatorFrontiers in cellular and infection microbiology · 2025Article
- Genomic insights into the 2022-2023Vibrio cholerae outbreak in Malawi.Nature communications · 2024Article
- Potential involvement of beta-lactamase homologous proteins in resistance to beta-lactam antibiotics in gram-negative bacteria of the ESKAPEE group.BMC genomics · 2024Article
- Genetic and Phenotypic Virulence Potential of Non-O1/Non-O139Microorganisms · 2023Article
- Complete genome sequence and comparative analysis of aFrontiers in microbiology · 2023Article
- Virulence and resistance patterns ofFrontiers in microbiology · 2023Article
- Characterization and Potentiating Effects of the Ethanolic Extracts of the Red SeaweedACS omega · 2022Article
- Insights into Carbapenem Resistance inInternational journal of molecular sciences · 2022Review
- Distribution, Phylogeny and Evolution of Clinical and EnvironmentalEvolutionary bioinformatics online · 2022Article
- Heatwave-associatedEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2021Article
- A Novel Cooperative Metallo-β-Lactamase Fold Metallohydrolase from Pathogen Vibrio vulnificus Exhibits β-Lactam Antibiotic-Degrading Activities.Antimicrobial agents and chemotherapy · 2021Article
- Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.Chemical reviews · 2021Review
- Vibrios from the Norwegian marine environment: Characterization of associated antibiotic resistance and virulence genes.MicrobiologyOpen · 2020Article
- Genome- and Proteome-Wide Analysis of Lysine Acetylation inFrontiers in microbiology · 2020Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The genome sequence of V. cholerae O1 Biovar Eltor strain N16961 has revealed a putative antibiotic resistance (var) regulon that is predicted to encode a transcriptional activator (VarR), which is divergently transcribed relative to the putative resistance genes for both a metallo-β-lactamase (VarG) and an antibiotic efflux-pump (VarABCDEF). We sought to test whether these genes could confer antibiotic resistance and are organised as a regulon under the control of VarR. VarG was overexpressed and purified and shown to have β-lactamase activity against penicillins, cephalosporins and carbapenems, having the highest activity against meropenem. The expression of VarABCDEF in the Escherichia coli (ΔacrAB) strain KAM3 conferred resistance to a range of drugs, but most significant resistance was to the macrolide spiramycin. A gel-shift analysis was used to determine if VarR bound to the promoter regions of the resistance genes. Consistent with the regulation of these resistance genes, VarR binds to three distinct intergenic regions, varRG, varGA and varBC located upstream and adjacent to varG, varA and varC, respectively. VarR can act as a repressor at the varRG promoter region; whilst this repression was relieved upon addition of β-lactams, these did not dissociate the VarR/varRG-DNA complex, indicating that the de-repression of varR by β-lactams is indirect. Considering that the genomic arrangement of VarR-VarG is strikingly similar to that of AmpR-AmpC system, it is possible that V. cholerae has evolved a system for resistance to the newer β-lactams that would prove more beneficial to the bacterium in light of current selective pressures.
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