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.
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 sequence;Bovine tuberculosis;Glycine;Mutation;Mycobacterium bovis;Mycobacterium tuberculosis;Polymerase chain reaction;Vaccines||DOI:||10.1371/journal.pone.0043467||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Veterinary Medicine Research Collection|
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