A Point Mutation in cycA Partially Contributes to the D-cycloserine Resistance Trait of Mycobacterium bovis BCG Vaccine Strains

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Title: A Point Mutation in cycA Partially Contributes to the D-cycloserine Resistance Trait of Mycobacterium bovis BCG Vaccine Strains
Authors: Chen, Jeffrey M.
Uplekar, Swapna
Gordon, Stephen V.
Cole, Stewart T.
Permanent link: http://hdl.handle.net/10197/5254
Date: Jan-2012
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.
Type of material: Journal Article
Publisher: Public Library of Science
Copyright (published version): 2012 the authors
Keywords: Amino acid sequenceBovine tuberculosisGlycineMutationMycobacterium bovisMycobacterium tuberculosisPolymerase chain reactionVaccines
DOI: 10.1371/journal.pone.0043467
Language: en
Status of Item: Peer reviewed
Appears in Collections:Veterinary Medicine Research Collection

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