title: Contribution of L-alanine dehydrogenase to in vivo persistence and protective efficacy of the BCG vaccine.
abstract: The tuberculosis (TB) vaccine strain Mycobacterium bovis BCG is unable to utilise alanine and this deficiency is thought to inhibit the growth of the vaccine in vivo and limit vaccine efficacy. In this report we demonstrate that L-alanine catabolism can be conferred on BCG by introduction of the gene encoding L-alanine dehydrogenase (Ald) of Mycobacterium tuberculosis. Restoration of Ald activity did not change the in vivo growth of BCG in macrophages or mice, and protection against aerosol M. tuberculosis infection was not altered by addition of ald to the BCG vaccine. These results demonstrate that the inability to utilise L-alanine is not a contributing factor to the attenuated phenotype of BCG and does not influence the protective efficacy of the vaccine against TB.
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW 2042, Australia.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Scandurra
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Ryan
authors.forename: Rachel
authors.initials: R
authors.lastname: Pinto
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
authors.forename: James A
authors.initials: JA
authors.lastname: Triccas
mesh_terms: D000409:Alanine / Q000378:metabolism; D050788:Alanine Dehydrogenase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D001483:Base Sequence; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D001500:BCG Vaccine; D014614:Vaccines, Synthetic; D050788:Alanine Dehydrogenase; D000409:Alanine