ArticleAntimicrobial agents and chemotherapy2012
Characterization of RarA, a novel AraC family multidrug resistance regulator in Klebsiella pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Plasmid-mediated quinolone resistance in Enterobacteriaceae: a systematic review with a focus on Mediterranean countries.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2017Pooled it
- Determination of frequency of spontaneous resistance for gepotidacin and levofloxacin against a collection of gram-positive and gram-negative organisms.Antimicrobial agents and chemotherapy · 2026Article
- Exploring differences in the human gut microbiome between Han Chinese and non-Chinese populations.Genome biology · 2026Article
- The CpxR-GlvR regulatory axis ofFrontiers in cellular and infection microbiology · 2026Article
- Unveiling structural dynamics and allosteric vulnerabilities in Klebsiella pneumoniae KPHS_11890: an integrated DRKG-MD study.Journal of computer-aided molecular design · 2025Article
- Bactericidal activity and Inhibition of levofloxacin-induced resistance by antibacterial combination against hypervirulent Klebsiella pneumoniae.Annals of clinical microbiology and antimicrobials · 2025Article
- Epidemiology and resistance mechanisms of tigecycline- and carbapenem-resistantFrontiers in microbiology · 2025Article
- Unlocking Nitrofurantoin: Understanding Molecular Mechanisms of Action and Resistance in Enterobacterales.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025Review
- The investigation of molecular epidemiological characteristics and resistance mechanism of tigecycline resistantFrontiers in cellular and infection microbiology · 2025Article
- Mechanisms of tigecycline resistance in Gram-negative bacteria: A narrative review.Engineering microbiology · 2024Review
- Mutations in the efflux regulator geneMicrobiology (Reading, England) · 2024Article
- Rapid evolution of colistin resistance in a bioreactor model of infection of Klebsiella pneumoniae.Communications biology · 2024Article
- Occurrence and mechanisms of tigecycline resistance in carbapenem- and colistin-resistant Klebsiella pneumoniae in Thailand.Scientific reports · 2024Article
- Article
- The tigecycline resistance mechanisms in Gram-negative bacilli.Frontiers in cellular and infection microbiology · 2024Review
- The Mar, Sox, and Rob Systems.EcoSal Plus · 2023Review
- Isolation and characterization of novel bacteriophage vB_KpP_HS106 forFrontiers in microbiology · 2023Article
- Genomic characterization of tigecycline-resistantFrontiers in microbiology · 2023Article
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives.Biological reviews of the Cambridge Philosophical Society · 2022Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Transcriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate the AcrAB efflux pump, have been shown to be associated with multidrug resistance in clinically relevant Gram-negative bacteria. In addition to the multidrug resistance phenotype, these regulators have also been shown to play a role in the cellular metabolism and possibly the virulence potential of microbial cells. As such, the increased expression of these proteins is likely to cause pleiotropic phenotypes. Klebsiella pneumoniae is a major nosocomial pathogen which can express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows that the increased transcription of ramA is associated with tigecycline resistance (M. Veleba and T. Schneiders, Antimicrob. Agents Chemother. 56:4466-4467, 2012). Bioinformatic analyses of the available Klebsiella genome sequences show that an additional AraC-type regulator is encoded chromosomally. In this work, we characterize this novel AraC-type regulator, hereby called RarA (Regulator of antibiotic resistance A), which is encoded in K. pneumoniae, Enterobacter sp. 638, Serratia proteamaculans 568, and Enterobacter cloacae. We show that the overexpression of rarA results in a multidrug resistance phenotype which requires a functional AcrAB efflux pump but is independent of the other AraC regulators. Quantitative real-time PCR experiments show that rarA (MGH 78578 KPN_02968) and its neighboring efflux pump operon oqxAB (KPN_02969_02970) are consistently upregulated in clinical isolates collected from various geographical locations (Chile, Turkey, and Germany). Our results suggest that rarA overexpression upregulates the oqxAB efflux pump. Additionally, it appears that oqxR, encoding a GntR-type regulator adjacent to the oqxAB operon, is able to downregulate the expression of the oqxAB efflux pump, where OqxR complementation resulted in reductions to olaquindox MICs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.