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Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis.

Festjens N, Bogaert P, Batni A, Houthuys E, Plets E, Vanderschaeghe D, Laukens B, Asselbergh B, Parthoens E, De Rycke R, Willart MA, Jacques P, Elewaut D, Brouckaert P, Lambrecht BN, Huygen K, Callewaert N - EMBO Mol Med (2011)

Bottom Line: Both systemic and intratracheal challenge of mice with Mycobacterium tuberculosis following vaccination showed that the SapM mutant, compared to the parental BCG vaccine, provided better protection: it led to longer-term survival.Persistence of the SapM-mutated BCG in vivo resembled that of the parental BCG indicating that this mutation will likely not compromise the safety of the BCG vaccine.The SapM mutant BCG vaccine was more effective than the parental vaccine in inducing recruitment and activation of CD11c(+) MHC-II(int) CD40(int) dendritic cells (DCs) to the draining lymph nodes.

View Article: PubMed Central - PubMed

Affiliation: Unit for Medical Biotechnology, Department for Molecular Biomedical Research, Ghent, Belgium. nele.festjens@dmbr.vib-ugent.be

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Uptake of M. bovis BCG WT and SapM mutants by BM-DCs and autophagy induction upon infectionBM-DCs were infected for 24 h with FITC-labelled mycobacteria (M. bovis BCG WT or SapM::T mutant, as indicated) at a MOI of 2. The number of FITC-positive DCs and mean FITC intensities are shown as averages and SEM of five independent experiments.BM-DCs (either pretreated with 10 µM rapamycin or not treated) were infected with M. bovis BCG WT or with SapM mutant at MOI of 2 and incubated at 37°C. After 24 h, cells were lysed and the expression of LC3 was revealed by western blot.
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fig03: Uptake of M. bovis BCG WT and SapM mutants by BM-DCs and autophagy induction upon infectionBM-DCs were infected for 24 h with FITC-labelled mycobacteria (M. bovis BCG WT or SapM::T mutant, as indicated) at a MOI of 2. The number of FITC-positive DCs and mean FITC intensities are shown as averages and SEM of five independent experiments.BM-DCs (either pretreated with 10 µM rapamycin or not treated) were infected with M. bovis BCG WT or with SapM mutant at MOI of 2 and incubated at 37°C. After 24 h, cells were lysed and the expression of LC3 was revealed by western blot.

Mentions: Similarly, we analysed the uptake of the parental M. bovis BCG and the SapM mutant by bone marrow-derived dendritic cells (BM-DCs). Again, WT M. bovis BCG and the SapM mutant were taken up by murine DCs with the same efficiency (Fig 3A).


Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis.

Festjens N, Bogaert P, Batni A, Houthuys E, Plets E, Vanderschaeghe D, Laukens B, Asselbergh B, Parthoens E, De Rycke R, Willart MA, Jacques P, Elewaut D, Brouckaert P, Lambrecht BN, Huygen K, Callewaert N - EMBO Mol Med (2011)

Uptake of M. bovis BCG WT and SapM mutants by BM-DCs and autophagy induction upon infectionBM-DCs were infected for 24 h with FITC-labelled mycobacteria (M. bovis BCG WT or SapM::T mutant, as indicated) at a MOI of 2. The number of FITC-positive DCs and mean FITC intensities are shown as averages and SEM of five independent experiments.BM-DCs (either pretreated with 10 µM rapamycin or not treated) were infected with M. bovis BCG WT or with SapM mutant at MOI of 2 and incubated at 37°C. After 24 h, cells were lysed and the expression of LC3 was revealed by western blot.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377067&req=5

fig03: Uptake of M. bovis BCG WT and SapM mutants by BM-DCs and autophagy induction upon infectionBM-DCs were infected for 24 h with FITC-labelled mycobacteria (M. bovis BCG WT or SapM::T mutant, as indicated) at a MOI of 2. The number of FITC-positive DCs and mean FITC intensities are shown as averages and SEM of five independent experiments.BM-DCs (either pretreated with 10 µM rapamycin or not treated) were infected with M. bovis BCG WT or with SapM mutant at MOI of 2 and incubated at 37°C. After 24 h, cells were lysed and the expression of LC3 was revealed by western blot.
Mentions: Similarly, we analysed the uptake of the parental M. bovis BCG and the SapM mutant by bone marrow-derived dendritic cells (BM-DCs). Again, WT M. bovis BCG and the SapM mutant were taken up by murine DCs with the same efficiency (Fig 3A).

Bottom Line: Both systemic and intratracheal challenge of mice with Mycobacterium tuberculosis following vaccination showed that the SapM mutant, compared to the parental BCG vaccine, provided better protection: it led to longer-term survival.Persistence of the SapM-mutated BCG in vivo resembled that of the parental BCG indicating that this mutation will likely not compromise the safety of the BCG vaccine.The SapM mutant BCG vaccine was more effective than the parental vaccine in inducing recruitment and activation of CD11c(+) MHC-II(int) CD40(int) dendritic cells (DCs) to the draining lymph nodes.

View Article: PubMed Central - PubMed

Affiliation: Unit for Medical Biotechnology, Department for Molecular Biomedical Research, Ghent, Belgium. nele.festjens@dmbr.vib-ugent.be

Show MeSH
Related in: MedlinePlus