Rifampicin Reduces Susceptibility to Ofloxacin in Rifampicin-resistant Mycobacterium tuberculosis through Efflux
Gail E. Louw,Robin M. Warren,Nicolaas C. Gey van Pittius,Rosalba Leon,Adelina Jimenez,Rogelio Hernández-Pando,Christopher R.E. McEvoy,Melanie Grobbelaar,Megan Murray,Paul D. van Helden,Thomas C. Victor +10 more
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TLDR
Exposure of rifampicin resistant M. tuberculosis strains to rifampsicin can potentially compromise the efficacy of the second-line treatment regimens containing ofloxacin, thereby emphasising the need for rapid diagnostics to guide treatment.Abstract:
Rationale: Central dogma suggests that rifampicin resistance in Mycobacterium tuberculosis develops solely through rpoB gene mutations.Objective: To determine whether rifampicin induces efflux pumps activation in rifampicin resistant M. tuberculosis strains thereby defining rifampicin resistance levels and reducing ofloxacin susceptibility.Methods: Rifampicin and/or ofloxacin minimum inhibitory concentrations (MICs) were determined in rifampicin resistant strains by culture in BACTEC 12B medium. Verapamil and reserpine were included to determine their effect on rifampicin and ofloxacin susceptibility. RT-qPCR was applied to assess expression of efflux pump/transporter genes after rifampicin exposure. To determine whether verapamil could restore susceptibility to first-line drugs, BALB/c mice were infected with a MDR-TB strain and treated with first-line drugs with/without verapamil.Measurements and Main Findings: Rifampicin MICs varied independently of rpoB mutation and genetic background. Addition reserp...read more
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Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy
Howard Takiff,Elba Guerrero +1 more
TL;DR: If fluoroquinolones are to be effectively employed in high-TB-burden regions their use for community-acquired pneumonias should be restricted, the prevalence of FQ-resistant TB should be monitored, and the cost of the treatment should be comparable to that of current standard drug regimens.
Journal ArticleDOI
Rifampicin-induced transcriptome response in rifampicin-resistant Mycobacterium tuberculosis.
Gerjo J. de Knegt,Oskar Bruning,Marian T. ten Kate,Mark de Jong,Alex van Belkum,Alex van Belkum,Hubert P. Endtz,Timo M. Breit,Irma A. J. M. Bakker-Woudenberg,Jurriaan E. M. de Steenwinkel +9 more
TL;DR: In this paper, the authors performed a genome-wide transcriptional profile analysis for Mycobacterium tuberculosis (M. tuberculosis) using microarray technology and qRT-PCR analysis.
Journal ArticleDOI
Redefining Multidrug-Resistant Tuberculosis Based on Clinical Response to Combination Therapy
TL;DR: Rifampin and isoniazid MICs improved the predictive capacity of the primary decision node by 20 and 17%, respectively, for these 36 patients, which is similar to those derived in clinical trial simulations.
Journal ArticleDOI
WhiB7, a transcriptional activator that coordinates physiology with intrinsic drug resistance in Mycobacterium tuberculosis
TL;DR: Drugs have been identified that inactivate resistance determinants in the whiB7 regulon, thereby potentiating the activities of diverse antibiotics against M. tuberculosis.
Journal ArticleDOI
Multimetallic Microparticles Increase the Potency of Rifampicin against Intracellular Mycobacterium tuberculosis
Timothy Ellis,Michele Chiappi,Andrés García-Trenco,Maryam Al-Ejji,Srijata Sarkar,Theoni K. Georgiou,Milo S. P. Shaffer,Teresa D. Tetley,Stephan Schwander,Mary P. Ryan,Alexandra E. Porter +10 more
TL;DR: In this paper, biodegradable multimetallic microparticles (MMPs), containing Ag NPs and ZnO NPs, were developed for use in pulmonary delivery of antituberculous drugs to the endosomal system of M.tb-infected macrophages.
References
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TL;DR: The crystal structure of Thermus aquaticus core RNAP complexed with Rif explains the effects of Rif on RNAP function and indicates that the inhibitor acts by directly blocking the path of the elongating RNA when the transcript becomes 2 to 3 nt in length.
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Amalio Telenti,P Imboden,F Marchesi,Lukas Matter,K Schopfer,Thomas Bodmer,Douglas B. Lowrie,M.J Colston,Stewart T. Cole +8 more
TL;DR: Substitution of a limited number of highly conserved aminoacids encoded by the rpoB gene appears to be the molecular mechanism responsible for "single step" high-level resistance to rifampicin in M tuberculosis, a marker of multidrug-resistant tuberculosis.
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