Genetic basis for natural and acquired resistance to the diarylquinoline R207910 in mycobacteria.
The atpE gene encoding the subunit c of the ATP synthase of Mycobacterium tuberculosis, the target of the new diarylquinoline drug R207910, has been sequenced from in vitro mutants resistant to the drug. The previously reported mutation A63P and a new mutation, I66M, were found. The genetic diversity of atpE in 13 mycobacterial species was also investigated, revealing that the region involved in resistance to R207910 is conserved, except in Mycobacterium xenopi in which the highly conserved residue Ala63 is replaced by Met, a modification that may be associated with the natural resistance of M. xenopi to R207910.
Petrella
Stephanie
S
Laboratoire de Recherche Moléculaire sur les Antibiotiques, LRMA INSERM U655, Université Pierre et Marie Curie, F-75634 Paris Cedex 13, France.
Cambau
Emmanuelle
E
Chauffour
Aurelie
A
Andries
Koen
K
Jarlier
Vincent
V
Sougakoff
Wladimir
W
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D064687:Diarylquinolines; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D007111:Immunity, Cellular; D008715:Methionine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D010802:Phylogeny; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
D000995:Antitubercular Agents; D064687:Diarylquinolines; D021122:Protein Subunits; D011804:Quinolines; C493870:bedaquiline; D008715:Methionine