Abstract
In mycobacteria, CycA a D-serine, L- and D-alanine, and glycine transporter also functions in the uptake of D-cycloserine, an important second-line anti-tubercular drug. A single nucleotide polymorphism identified in the cycA gene of BCG was hypothesized to contribute to the increased resistance of Mycobacterium bovis bacillus Calmette-Guérin (BCG) to D-cycloserine compared to wild-type Mycobacterium tuberculosis or Mycobacterium bovis. Working along these lines, a merodiploid strain of BCG expressing Mycobacterium tuberculosis CycA was generated and found to exhibit increased susceptibility to D-cycloserine albeit not to the same extent as wild-type Mycobacterium tuberculosis or Mycobacterium bovis. In addition, recombinant Mycobacterium smegmatis strains expressing either Mycobacterium tuberculosis or Mycobacterium bovis CycA but not BCG CycA were rendered more susceptible to D-cycloserine. These findings support the notion that CycA-mediated uptake in BCG is impaired as a result of a single nucleotide polymorphism; however, the partial contribution of this impairment to D-cycloserine resistance suggests the involvement of additional genetic lesions in this phenotype.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Transport Systems, Neutral / chemistry
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Amino Acid Transport Systems, Neutral / genetics*
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Amino Acid Transport Systems, Neutral / metabolism
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Antibiotics, Antitubercular / pharmacology
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BCG Vaccine / immunology
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics*
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Bacterial Proteins / metabolism
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Base Sequence
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Cycloserine / chemistry
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Cycloserine / pharmacology*
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Drug Resistance, Bacterial / genetics*
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Gene Knock-In Techniques
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Microbial Sensitivity Tests
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Microbial Viability / drug effects
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Microbial Viability / genetics
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Models, Molecular
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Molecular Sequence Data
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Mycobacterium bovis / genetics*
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Mycobacterium bovis / immunology
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Mycobacterium bovis / metabolism
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Mycobacterium smegmatis / genetics
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Mycobacterium smegmatis / growth & development
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Mycobacterium smegmatis / metabolism
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Point Mutation*
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Polymorphism, Single Nucleotide
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Protein Structure, Secondary
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Sequence Homology, Amino Acid
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Symporters / chemistry
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Symporters / genetics*
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Symporters / metabolism
Substances
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Amino Acid Transport Systems, Neutral
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Antibiotics, Antitubercular
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BCG Vaccine
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Bacterial Proteins
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Symporters
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Cycloserine