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Mem. Inst. Oswaldo Cruz ; 113(11): e180267, 2018. graf
Artículo en Inglés | LILACS | ID: biblio-1040585

RESUMEN

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.


Asunto(s)
Humanos , Transcripción Genética/genética , Vacuna BCG/farmacología , Supervivencia Celular/genética , Citocinas/efectos de los fármacos , Mutación con Ganancia de Función/genética , Macrófagos/microbiología , Mycobacterium bovis/genética , Factores de Tiempo , Transcripción Genética/efectos de los fármacos , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/microbiología , Vacuna BCG/genética , Supervivencia Celular/efectos de los fármacos , Citocinas/genética , Mutación con Ganancia de Función/efectos de los fármacos , Mycobacterium bovis/fisiología
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