Inhibition of RNA Polymerase by Rifampicin and Rifamycin-Like Molecules

RNA polymerases (RNAPs) accomplish the first step of gene expression in all living organisms. However, the sequence divergence between bacterial and human RNAPs makes the bacterial RNAP a promising target for antibiotic development. The most clinically important and extensively studied class of antibiotics known to inhibit bacterial RNAP are the rifamycins. For example, rifamycins are a vital element of the current combination therapy for treatment of tuberculosis. Here, we provide an overview of the history of the discovery of rifamycins, their mechanisms of action, the mechanisms of bacterial resistance against them, and progress in their further development.

• Publication year

  2020

• Venue

  EcoSal Plus

• Publication date

  2020-03-20

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1128/ecosalplus.esp-0017-2019PMID 32342856PMCID PMC11168578
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Mechanisms of antibiotics inhibiting bacterial RNA polymerase.

  2019cited by this paper
• Comment on: The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis.

  2018cited by this paper
• An Introduction to the Structure and Function of the Catalytic Core Enzyme of Escherichia coli RNA Polymerase

  2018cited by this paper
• Mode of Action of Kanglemycin A, an Ansamycin Natural Product that Is Active against Rifampicin-Resistant Mycobacterium tuberculosis

  2018cited by this paper
• Rifamycin congeners kanglemycins are active against rifampicin-resistant bacteria via a distinct mechanism

  2018cited by this paper
• The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis

  2018cited by this paper
• Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase: pseudouridimycin

  2017cited by this paper
• Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates

  2017cited by this paper
• Structural basis for rifamycin resistance of bacterial RNA polymerase by the three most clinically important RpoB mutations found in Mycobacterium tuberculosis

  2017cited by this paper
• Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition.

  2017cited by this paper
• Rifampicin-Resistance Mutations in the rpoB Gene in Bacillus velezensis CC09 have Pleiotropic Effects

  2017cited by this paper
• Intrinsic rifamycin resistance of Mycobacterium abscessus is mediated by ADP-ribosyltransferase MAB_0591

  2017cited by this paper
• Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex.

  2016cited by this paper
• Comprehensive phenotypic characterization of rifampicin resistance mutations in Salmonella provides insight into the evolution of resistance in Mycobacterium tuberculosis.

  2015cited by this paper
• Study of efflux pump gene expression in rifampicin-monoresistant Mycobacterium tuberculosis clinical isolates

  2015cited by this paper
• Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015.

  2015cited by this paper
• Distinct functions of the RNA polymerase σ subunit region 3.2 in RNA priming and promoter escape

  2014cited by this paper
• Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the β′ subunit of RNA polymerase

  2014cited by this paper
• Modification of Rifamycin Polyketide Backbone Leads to Improved Drug Activity against Rifampicin-resistant Mycobacterium tuberculosis*

  2014cited by this paper
• Resistance to rifampicin: a review

  2014cited by this paper
• Rifampicin Resistance: Fitness Costs and the Significance of Compensatory Evolution

  2013cited by this paper
• The σ70 region 1.2 regulates promoter escape by unwinding DNA downstream of the transcription start site

  2013cited by this paper
• Evolution of Escherichia coli rifampicin resistance in an antibiotic-free environment during thermal stress

  2013cited by this paper
• X-ray crystal structures of the Escherichia coli RNA polymerase in complex with benzoxazinorifamycins.

  2013cited by this paper
• Genetic characterization of compensatory evolution in strains carrying rpoB Ser531Leu, the rifampicin resistance mutation most frequently found in clinical isolates.

  2013cited by this paper
• Fitness‐compensatory mutations in rifampicin‐resistant RNA polymerase

  2012cited by this paper
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  2012cited by this paper
• Rifaximin Resistance in Escherichia coli Associated with Inflammatory Bowel Disease Correlates with Prior Rifaximin Use, Mutations in rpoB, and Activity of Phe-Arg-β-Naphthylamide-Inhibitable Efflux Pumps

  2012cited by this paper
• Structure-based design of novel benzoxazinorifamycins with potent binding affinity to wild-type and rifampin-resistant mutant Mycobacterium tuberculosis RNA polymerases.

  2012cited by this paper
• Rifamycin inhibition of WT and Rif-resistant Mycobacterium tuberculosis and Escherichia coli RNA polymerases in vitro.

  2011cited by this paper
• Whole-genome sequencing of rifampicin-resistant M. tuberculosis strains identifies compensatory mutations in RNA polymerase

  2011cited by this paper
• Strong In Vitro Activities of Two New Rifabutin Analogs against Multidrug-Resistant Mycobacterium tuberculosis

  2010cited by this paper
• Antibiotic resistance and its cost: is it possible to reverse resistance?

  2010cited by this paper
• Rifamycins--obstacles and opportunities.

  2010cited by this paper
• Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance

  2010cited by this paper
• Tuberculosis Drug Resistance Mutation Database

  2009cited by this paper
• Development of Escherichia coli rifaximin-resistant mutants: frequency of selection and stability.

  2008cited by this paper
• Rifalazil Retains Activity Against Rifampin-resistant Mutants of Chlamydia pneumoniae

  2008cited by this paper
• Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center

  2008cited by this paper
• Update on Rifampin and Rifabutin Drug Interactions

  2008cited by this paper
• New C25 carbamate rifamycin derivatives are resistant to inactivation by ADP-ribosyl transferases.

  2007cited by this paper
• In Vitro Activities of Different Inhibitors of Bacterial Transcription against Staphylococcus epidermidis Biofilm

  2007cited by this paper
• Molecular Genetic and Structural Modeling Studies of Staphylococcus aureus RNA Polymerase and the Fitness of Rifampin Resistance Genotypes in Relation to Clinical Prevalence

  2006cited by this paper
• The Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis

  2006cited by this paper
• Is It Easy to Stop RNA Polymerase?

  2006cited by this paper
• New rifabutin analogs: synthesis and biological activity against Mycobacterium tuberculosis.

  2006cited by this paper
• Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders.

  2006cited by this paper
• Rifamycin-mode of action, resistance, and biosynthesis.

  2005cited by this paper
• Mechanism of natural rifampin resistance of Streptomyces spp.

  2005cited by this paper
• Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins.

  2005cited by this paper
• Different Rifampin Sensitivities of Escherichia coli and Mycobacterium tuberculosis RNA Polymerases Are Not Explained by the Difference in the β-Subunit Rifampin Regions I and II

  2005cited by this paper
• The role of RNA polymerase sigma subunit in promoter-independent initiation of transcription.

  2004cited by this paper
• The role of RNA polymerase σ subunit in promoter-independent initiation of transcription

  2004cited by this paper
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  2004cited by this paper
• Effect of rpoB Mutations Conferring Rifampin Resistance on Fitness of Mycobacterium tuberculosis

  2004cited by this paper
• In vitro and in vivo activities of new rifamycin derivatives against mycobacterial infections.

  2004cited by this paper
• Structural mechanism for rifampicin inhibition of bacterial rna polymerase.

  2001cited by this paper
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• Recombinant Thermus aquaticus RNA Polymerase, a New Tool for Structure-Based Analysis of Transcription

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  2000cited by this paper
• Accumulation of rifampicin by Mycobacterium aurum, Mycobacterium smegmatis and Mycobacterium tuberculosis.

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• Mutations in the Beginning of the rpoBGene Can Induce Resistance to Rifamycins in both Helicobacter pylori and Mycobacterium tuberculosis

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• Comparison of the in vitro activities of rifapentine and rifampicin against Mycobacterium tuberculosis complex.

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• Compensatory evolution in rifampin-resistant Escherichia coli.

  2000cited by this paper
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  1999cited by this paper
• Physiological Cost of Rifampin Resistance Induced In Vitro in Mycobacterium tuberculosis

  1999cited by this paper
• The biological cost of antibiotic resistance.

  1999cited by this paper
• Rifapentine: Its Role in the Treatment of Tuberculosis

  1999cited by this paper
• Rifampin and Rifabutin Resistance Mechanism inHelicobacter pylori

  1999cited by this paper
• Virulence of antibiotic-resistant Salmonella typhimurium.

  1998cited by this paper
• Contribution of rpoB Mutations to Development of Rifamycin Cross-Resistance in Mycobacterium tuberculosis

  1998cited by this paper
• Comprehensive study on structure-activity relationships of rifamycins: discussion of molecular and crystal structure and spectroscopic and thermochemical properties of rifamycin O.

  1998cited by this paper
• Effect of a new rifamycin derivative, rifalazil, on liver microsomal enzyme induction in rat and dog.

  1998cited by this paper
• Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis.

  1998cited by this paper
• Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update.

  1998cited by this paper
• Rifampicin resistance in Neisseria meningitidis: evidence from a study of sibling strains, description of new mutations and notes on population genetics.

  1997cited by this paper
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  1996cited by this paper
• The β Subunit Rif-cluster I Is Only Angstroms Away from the Active Center of Escherichia coli RNA Polymerase *

  1995cited by this paper
• In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible and multidrug-resistant tubercle bacilli

  1995cited by this paper
• Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648

  1995cited by this paper
• cAMP-dependent SOS induction and mutagenesis in resting bacterial populations.

  1995cited by this paper
• Topology of the RNA polymerase active center probed by chimeric rifampicin-nucleotide compounds.

  1994cited by this paper
• RifR mutations in the beginning of the Escherichia coli rpoB gene

  1994cited by this paper
• In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives

  1994cited by this paper
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  1993cited by this paper
• Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives.

  1993cited by this paper
• Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis.

  1993cited by this paper
• Rifampicin region revisited. New rifampicin-resistant and streptolydigin-resistant mutants in the beta subunit of Escherichia coli RNA polymerase.

  1993cited by this paper
• Two New Genera of Nocardioform Actinomycetes: Amycolata gen. nov. and Amycolatopsis gen. nov.

  1986cited by this paper
• A study of structure-activity relationships in 4-deoxypyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV derivatives by electron spectroscopy for chemical analysis and 1H NMR.

  1985cited by this paper
• Correlation of structure and activity in ansamycins. Molecular structure of sodium rifamycin SV.

  1983cited by this paper
• History of the development of rifampin.

  1983cited by this paper
• Structure-activity relationships in the ansamycins. Molecular structure and activity of 3-carbomethoxy rifamycin S.

  1982cited by this paper
• Antibacterial activity of DL 473, a new semisynthetic rifamycin derivative.

  1981cited by this paper
• Synthesis and antibacterial activity of some ester, amides, and hydrazides of 3-carboxyrifamycin S. Relationship between structure and activity of ansamycins.

  1981cited by this paper
• Biological activity of a new class of rifamycins. Spiro-piperidyl-rifamycins.

  1980cited by this paper
• Structure-activity relationships in the ansamycins: the crystal structure of tolypomycinone.

  1978cited by this paper
• A new tolypomycin-Y derivative: in vitro and in vivo antimicrobial activity.

  1978cited by this paper
• On the mechanism of rifampicin inhibition of RNA synthesis.

  1978cited by this paper

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