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

Creator:

Chen, Jeffrey M.; Uplekar, Swapna; Gordon, Stephen V.; Cole, Stewart T.;

Institution: Public Library of Science
Subject Keywords: Amino acid sequence; Bovine tuberculosis; Glycine; Mutation; Mycobacterium bovis; Mycobacterium tuberculosis; Polymerase chain reaction; Vaccines;
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Description:

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.

Related: http://dx.doi.org/10.1371/journal.pone.0043467
Suggested citation:

Chen, Jeffrey M.; Uplekar, Swapna; Gordon, Stephen V.; Cole, Stewart T.; . () A Point Mutation in cycA Partially Contributes to the D-cycloserine Resistance Trait of Mycobacterium bovis BCG Vaccine Strains [Online]. Available from: http://publichealthwell.ie/node/773028 [Accessed: 21st September 2019].

  

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