Cross-resistance between rifampicin and KRM-1648 is associated with specific rpoB alleles in Mycobacterium tuberculosis.
KRM-1648 resistant Mycobacterium tuberculosis strains were identified from a collection of rifampicin-resistant strains. Several strains had novel rpoB gene mutations in codons 512, 529 and 533 of the rpoB gene. The strains with mutations in codons 526 or 531, major mutation sites in rifampicin-resistant M. tuberculosis, were resistant to KRM-1648. Also, the strains with other mutations in the rpoB gene that were initially susceptible to KRM-1648 were prone to developing KRM-1648 resistance after further mutation. Thus, KRM-1648 is unlikely to be useful for the treatment of rifampicin-resistant tuberculosis.
Park
Y K
YK
Korean Institute of Tuberculosis, Korean National Tuberculosis Association, Seoul.
Kim
B J
BJ
Ryu
S
S
Kook
Y H
YH
Choe
Y K
YK
Bai
G H
GH
Kim
S J
SJ
D000483:Alleles; D001483:Base Sequence; D004269:DNA, Bacterial / Q000032:analysis*; D012321:DNA-Directed RNA Polymerases / Q000032:analysis / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012293:Rifampin / Q000494:pharmacology*; D012294:Rifamycins / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA
D004269:DNA, Bacterial; D012294:Rifamycins; C068980:KRM 1648; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin