title: Clinical isolates of Mycobacterium tuberculosis in four European hospitals are uniformly susceptible to benzothiazinones.
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.
authors.affiliation: University of Pavia, Department of Genetics and Microbiology, Via Ferrata 1, 27100 Pavia, Italy. m.pasca@ipvgen.unipv.it
authors.forename: Maria Rosalia
authors.initials: MR
authors.lastname: Pasca
authors.forename: Giulia
authors.initials: G
authors.lastname: Degiacomi
authors.forename: Ana Luisa de Jesus Lopes
authors.initials: AL
authors.lastname: Ribeiro
authors.forename: Francesca
authors.initials: F
authors.lastname: Zara
authors.forename: Patrizia
authors.initials: P
authors.lastname: De Mori
authors.forename: Beate
authors.initials: B
authors.lastname: Heym
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mirrione
authors.forename: Roberto
authors.initials: R
authors.lastname: Brerra
authors.forename: Laura
authors.initials: L
authors.lastname: Pagani
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Pucillo
authors.forename: Panajota
authors.initials: P
authors.lastname: Troupioti
authors.forename: Vadim
authors.initials: V
authors.lastname: Makarov
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
authors.forename: Giovanna
authors.initials: G
authors.lastname: Riccardi
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005060:Europe; D005798:Genes, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification*; D019998:Racemases and Epimerases / Q000235:genetics; D013141:Spiro Compounds / Q000494:pharmacology*; D013843:Thiazines / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: C540716:2-(2-methyl-1,4-dioxa-8-azaspiro(4.5)dec-8-yl)-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one; D000995:Antitubercular Agents; D017931:DNA Primers; D004269:DNA, Bacterial; D013141:Spiro Compounds; D013843:Thiazines; D019998:Racemases and Epimerases