ArticleAntimicrobial agents and chemotherapy2013
Elucidating the regulon of multidrug resistance regulator RarA in Klebsiella pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- Epidemiology and resistance mechanisms of tigecycline- and carbapenem-resistantFrontiers in microbiology · 2025Article
- Role of bacterial multidrug efflux pumps during infection.World journal of microbiology & biotechnology · 2024Review
- Plant-Origin Components: New Players to Combat Antibiotic Resistance inInternational journal of molecular sciences · 2024Review
- Synergistic effects of polymyxin and vancomycin combinations on carbapenem- and polymyxin-resistantMicrobiology spectrum · 2023Article
- Impact ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Evidence for Complex Interplay between Quorum Sensing and Antibiotic Resistance in Pseudomonas aeruginosa.Microbiology spectrum · 2022Article
- Antimicrobial activity of clioquinol and nitroxoline: a scoping review.Archives of microbiology · 2022Article
- Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2022Review
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Emergence of a Hypervirulent Tigecycline-ResistantFrontiers in microbiology · 2022Article
- Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2021Review
- Evaluation of gene expression and protein structural modeling involved in persister cell formation in Salmonella Typhimurium.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021Article
- The Characteristic of Virulence, Biofilm and Antibiotic Resistance ofInternational journal of environmental research and public health · 2020Review
- An Intertwined Network of Regulation Controls Membrane Permeability Including Drug Influx and Efflux in Enterobacteriaceae.Microorganisms · 2020Review
- Rapid antibiotic susceptibility testing based on bacterial motion patterns with long short-term memory neural networks.IEEE sensors journal · 2020Article
- Development of Tigecycline Resistance in Carbapenemase-ProducingAnnals of laboratory medicine · 2020Article
- Prevalence and phenotypic characterization of carbapenem-resistantInfection and drug resistance · 2019Article
- The nature and epidemiology of OqxAB, a multidrug efflux pump.Antimicrobial resistance and infection control · 2019Review
- Effective targeted therapy for drug-resistant infection by ICAM-1 antibody-conjugated TPGS modified β-GaTheranostics · 2019Article
- Contribution of OqxAB Efflux Pump in Selection of Fluoroquinolone-ResistantThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2018Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
RarA is an AraC-type regulator in Klebsiella pneumoniae, which, when overexpressed, confers a low-level multidrug-resistant (MDR) phenotype linked to the upregulation of both the acrAB and oqxAB efflux genes. Increased rarA expression has also been shown to be integral in the development of tigecycline resistance in the absence of ramA in K. pneumoniae. Given its phenotypic role in MDR, microarray analyses were performed to determine the RarA regulon. Transcriptome analysis was undertaken using strains Ecl8ΔrarA/pACrarA-2 (rarA-expressing construct) and Ecl8ΔrarA/pACYC184 (vector-only control) using bespoke microarray slides consisting of probes derived from the genomic sequences of K. pneumoniae MGH 78578 (NC_009648.1) and Kp342 (NC_011283.1). Our results show that rarA overexpression resulted in the differential expression of 66 genes (42 upregulated and 24 downregulated). Under the COG (clusters of orthologous groups) functional classification, the majority of affected genes belonged to the category of cell envelope biogenesis and posttranslational modification, along with genes encoding the previously uncharacterized transport proteins (e.g., KPN_03141, sdaCB, and leuE) and the porin OmpF. However, genes associated with energy production and conversion and amino acid transport/metabolism (e.g., nuoA, narJ, and proWX) were found to be downregulated. Biolog phenotype analyses demonstrated that rarA overexpression confers enhanced growth of the overexpresser in the presence of several antibiotic classes (i.e., beta-lactams and fluoroquinolones), the antifungal/antiprotozoal compound clioquinol, disinfectants (8-hydroxyquinoline), protein synthesis inhibitors (i.e., minocycline and puromycin), membrane biogenesis agents (polymyxin B and amitriptyline), DNA synthesis (furaltadone), and the cytokinesis inhibitor (sanguinarine). Both our transcriptome and phenotypic microarray data support and extend the role of RarA in the MDR phenotype of K. pneumoniae.
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