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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Dissertation
Caracterização fenotípica e genotípica de Mycobacterium tuberculosis da família Beijing do tipo ancestral e moderno
TL;DR: Genetically and phenotypically Mtb Beijing strains: eight sporadic isolates circulating in Brazil and eighteen isolated from regions with more prevalence, as Mozambique and Russia are characterized.
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Regulatory responses to rifampicin exposure in Mycobacterium tuberculosis
TL;DR: Advances in the study of the mycobacterial ETC are detail, which suggests that energy metabolism and ATP production through the PMF, which is established by the electron transport chain (ETC), are critical in determining the drug susceptibility of M. tuberculosis.
Journal ArticleDOI
Is the efflux pump inhibitor Verapamil a potential booster for isoniazid against Mycobacterium tuberculosis
Renata Claro Ribeiro do Amaral,Katiany Rizzieri Caleffi-Ferracioli,Fernanda de Oliveira Demitto,Aryadne Larissa de Almeida,Vera Lúcia Dias Siqueira,Regiane Bertin de Lima Scodro,Clarice Queico Fujimura Leite,Fernando Rogério Pavan,Rosilene Fressatti Cardoso +8 more
TL;DR: In vitro interaction of Verapamil (VP), an efflux pump inhibitor, with the classical first-line anti-tuberculosis drug isoniazid (INH) in resistant and susceptible M. tuberculosis clinical isolates is investigated.
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Inhaled anti-tubercular therapy: Dry powder formulations, device and toxicity challenges
TL;DR: This document summarizes current capabilities, research and operational priorities, and plans for further studies that were established at the 2015 USGS workshop on quantitative hazard assessments of earthquake-triggered landsliding and liquefaction in the Central American region.
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Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against Mycobacterium tuberculosis Infection
TL;DR: Interestingly, orally administered febuxostat was efficacious in a murine model of TB with reduced bacterial loads in both the lung and spleen without the exacerbation of lung inflammation, which highlights the drug potency.
References
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Stewart T. Cole,Roland Brosch,Julian Parkhill,Thierry Garnier,Carol Churcher,David Harris,Stephen V. Gordon,Karin Eiglmeier,S. Gas,Clifton E. Barry,Fredj Tekaia,K. Badcock,D. Basham,D. Brown,Tracey Chillingworth,R. Connor,Robert L. Davies,K. Devlin,Theresa Feltwell,S. Gentles,N. Hamlin,S. Holroyd,T. Hornsby,Kay Jagels,Anders Krogh,J. McLean,Sharon Moule,Lee Murphy,K. Oliver,J. Osborne,Michael A. Quail,Marie-Adèle Rajandream,Jane Rogers,S. Rutter,K. Seeger,Jason Skelton,Rob Squares,S. Squares,John Sulston,K. Taylor,Sally Whitehead,Bart Barrell +41 more
TL;DR: The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve the understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions.
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Structural Mechanism for Rifampicin Inhibition of Bacterial RNA Polymerase
Elizabeth A. Campbell,Nataliya Korzheva,Arkady Mustaev,Katsuhiko S. Murakami,Satish K. Nair,Alex Goldfarb,Seth A. Darst +6 more
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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Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis
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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The ATP binding cassette (ABC) transport systems of Mycobacterium tuberculosis
Martine Braibant,Philippe Gilot +1 more
TL;DR: The inventory and assembly of the typical subunits of the ABC transporters encoded by the complete genome of Mycobacterium tuberculosis found that there is an under-representation of the importers in M. tuberculosis, which may reflect the capacity of this bacterium to synthesize many essential compounds and to grow in the presence of few external nutrients.
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Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis.
TL;DR: The fluctuation test shows that Mycobacterium tuberculosis mutates to resistance to isoniazid, streptomycin, ethambutol and rifampin spontaneously and at random.