Gain of function in Mycobacterium bovis BCG Moreau due to loss of a transcriptional repressor
Mem. Inst. Oswaldo Cruz
;
113(11): e180267, 2018. graf
Artículo
en Inglés
| LILACS
| ID: biblio-1040585
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.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Transcripción Genética
/
Vacuna BCG
/
Supervivencia Celular
/
Citocinas
/
Mutación con Ganancia de Función
/
Macrófagos
/
Mycobacterium bovis
Límite:
Humanos
Idioma:
Inglés
Revista:
Mem. Inst. Oswaldo Cruz
Asunto de la revista:
Medicina Tropical
/
Parasitología
Año:
2018
Tipo del documento:
Artículo
País de afiliación:
Brasil
Institución/País de afiliación:
Fundação Oswaldo Cruz-Fiocruz/BR
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