Gain of function in Mycobacterium bovis BCG Moreau due to loss of a transcriptional repressor
Mem. Inst. Oswaldo Cruz
; 113(11): e180267, 2018. graf
Article
in English
| LILACS
| ID: biblio-1040585
Responsible library:
BR1.1
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.
Full text:
Available
Collection:
International databases
Health context:
Neglected Diseases
Health problem:
Neglected Diseases
/
Tuberculosis
/
Zoonoses
Database:
LILACS
Main subject:
Transcription, Genetic
/
BCG Vaccine
/
Cell Survival
/
Cytokines
/
Gain of Function Mutation
/
Macrophages
/
Mycobacterium bovis
Limits:
Humans
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2018
Document type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Fundação Oswaldo Cruz-Fiocruz/BR