Abstract
The new antitubercular drug candidate 2-[2-S-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one (BTZ043) targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase. To monitor the potential development of benzothiazinone (BTZ) resistance, a total of 240 sensitive and multidrug-resistant Mycobacterium tuberculosis clinical isolates from four European hospitals were surveyed for the presence of mutations in the dprE1 gene and for BTZ susceptibility. All 240 strains were susceptible, thus establishing the baseline prior to the introduction of BTZ043 in clinical trials.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antitubercular Agents / pharmacology*
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Base Sequence
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DNA Primers / genetics
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DNA, Bacterial / genetics
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Drug Resistance, Multiple, Bacterial / genetics
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Europe
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Genes, Bacterial
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Humans
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In Vitro Techniques
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Microbial Sensitivity Tests
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Mutation
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / enzymology
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / isolation & purification*
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Racemases and Epimerases / genetics
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Spiro Compounds / pharmacology*
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Thiazines / pharmacology*
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Tuberculosis, Multidrug-Resistant / drug therapy*
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Tuberculosis, Multidrug-Resistant / microbiology*
Substances
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2-(2-methyl-1,4-dioxa-8-azaspiro(4.5)dec-8-yl)-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one
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Antitubercular Agents
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DNA Primers
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DNA, Bacterial
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Spiro Compounds
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Thiazines
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Racemases and Epimerases