Clinical isolates of Mycobacterium tuberculosis in four European hospitals are uniformly susceptible to benzothiazinones.
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.
Pasca
Maria Rosalia
MR
University of Pavia, Department of Genetics and Microbiology, Via Ferrata 1, 27100 Pavia, Italy. m.pasca@ipvgen.unipv.it
Degiacomi
Giulia
G
Ribeiro
Ana Luisa de Jesus Lopes
AL
Zara
Francesca
F
De Mori
Patrizia
P
Heym
Beate
B
Mirrione
Maurizio
M
Brerra
Roberto
R
Pagani
Laura
L
Pucillo
Leopoldo
L
Troupioti
Panajota
P
Makarov
Vadim
V
Cole
Stewart T
ST
Riccardi
Giovanna
G
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*
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