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GAIN OF FUNCTION IN MYCOBACTERIUM BOVIS BCG MOREAU DUE TO LOSS OF A TRANSCRIPTIONAL REPRESSOR
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Abstract
The Bacille Calmette-Guérin (BCG) vaccine comprises a family of genetically different strains derived by the loss of
genomic regions (RDs) and other mutations. In BCG Moreau, loss of RD16 inactivates rv3405c*, encoding a transcriptional
repressor that negatively regulates the expression of Rv3406, an alkyl sulfatase. To evaluate the impact of this loss on the BCG
and host cell viability and the cytokine profile, THP-1 cells were infected with BCG Moreau (harbouring the empty vector) and
a complemented strain carrying a functional copy of rv3405c. Viability of the host cells and bacteria as well as the pattern of
cytokine secretion were evaluated. Our results show that the viability of BCG Moreau is higher than that of the complemented
strain in an axenic medium, suggesting a possible functional gain associated with the constitutive expression of Rv3406.
Viability of the host cells did not vary significantly between recombinant strains, but differences in the profiles of the cytokine
secretion (IL-1β and IL-6) were observed. Our results suggest an example of a functional gain due to gene loss contributing to
the elucidation of the impact of RD16 on the physiology of BCG Moreau.
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