EmbCAB operon of mycobacteria and mutants thereof

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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435 6, 435 911, 435863, 536 231, 536 2432, C07H 2104, C07H 2102, C12Q 168, C12P 1934

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active

060158905

ABSTRACT:
This invention relates to the identification, cloning, sequencing and characterization of the embCAB operon which determines mycobacterial resistance to the antimycobacterial drug ethambutol. The embCAB operon encodes the proteins which are the target of action of Mycobacterium tuberculosis, Mycobacterium smegmatis, and Mycobacterium leprae for ethambutol. The present invention provides purified and isolated embC, embA, and embB nucleic acids which comprise the embCAB operon, as well as mutated forms of these nucleic acids. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the wild type embCAB operon or the mutated embCAB operon, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of drug-resistant mycobacterial strain. The present invention also provides methods for the treatment and prevention of mycobacterial infections. In addition, the probes of the present invention may be used to determine the susceptibility of mycobacteria to ethambutol.

REFERENCES:
Belanger et al, "The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol", Proc. Natl. Acad. Sci. USA, vol. 93, pp. 11919-11924, Oct. 1, 1996.
Telenti et al, Mycobacterium smegmatis ethambutol resistance region: EmbC (embC) gene, partial cds, EmbA (emba) and embB (embG) genes, complete cds., direct submission to GenBank data base, accession No. U46844, Feb. 20, 1996.

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