| http://purl.uniprot.org/citations/9260945 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/9260945 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/9260945 | http://www.w3.org/2000/01/rdf-schema#comment | "D-Cycloserine is an effective second-line drug against Mycobacterium avium and Mycobacterium tuberculosis. To analyze the genetic determinants of D-cycloserine resistance in mycobacteria, a library of a resistant Mycobacterium smegmatis mutant was constructed. A resistant clone harboring a recombinant plasmid with a 3.1-kb insert that contained the glutamate decarboxylase (gadA) and D-alanine racemase (alrA) genes was identified. Subcloning experiments demonstrated that alrA was necessary and sufficient to confer a D-cycloserine resistance phenotype. The D-alanine racemase activities of wild-type and recombinant M. smegmatis strains were inhibited by D-cycloserine in a concentration-dependent manner. The D-cycloserine resistance phenotype in the recombinant clone was due to the overexpression of the wild-type alrA gene in a multicopy vector. Analysis of a spontaneous resistant mutant also demonstrated overproduction of wild-type AlrA enzyme. Nucleotide sequence analysis of the overproducing mutant revealed a single transversion (G-->T) at the alrA promoter, which resulted in elevated beta-galactosidase reporter gene expression. Furthermore, transformants of Mycobacterium intracellulare and Mycobacterium bovis BCG carrying the M. smegmatis wild-type alrA gene in a multicopy vector were resistant to D-cycloserine, suggesting that AlrA overproduction is a potential mechanism of D-cycloserine resistance in clinical isolates of M. tuberculosis and other pathogenic mycobacteria. In conclusion, these results show that one of the mechanisms of D-cycloserine resistance in M. smegmatis involves the overexpression of the alrA gene due to a promoter-up mutation."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.org/dc/terms/identifier | "doi:10.1128/jb.179.16.5046-5055.1997"xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.org/dc/terms/identifier | "doi:10.1128/jb.179.16.5046-5055.1997"xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Feng Z."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Feng Z."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Kapur V."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Kapur V."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Barletta R.G."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Barletta R.G."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Caceres N.E."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Caceres N.E."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Harris N.B."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Harris N.B."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Wellehan J.F."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/author | "Wellehan J.F."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/date | "1997"xsd:gYear |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/date | "1997"xsd:gYear |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/name | "J. Bacteriol."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/name | "J. Bacteriol."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/pages | "5046-5055"xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/pages | "5046-5055"xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/title | "Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine in Mycobacterium smegmatis."xsd:string |
| http://purl.uniprot.org/citations/9260945 | http://purl.uniprot.org/core/title | "Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine in Mycobacterium smegmatis."xsd:string |