Advanced search
Start date
Betweenand

Systems and comparative biology of Mycobacterium tuberculosis complex: effects of genetic variability on bacterial phenotype

Grant number: 16/26108-0
Support type:Research Grants - Young Investigators Grants
Duration: December 01, 2017 - November 30, 2021
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Ana Marcia de Sá Guimarães
Grantee:Ana Marcia de Sá Guimarães
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo, SP, Brazil
Assoc. researchers:Lucas Miranda Marques ; Maria Regina D'Império Lima
Associated scholarship(s):18/05562-0 - Comparative study of the immune response of the human macrophage infected with different species of the Mycobacterium tuberculosis complex, BP.MS
17/04617-3 - Host adaption of Mycobacterium tuberculosis and Mycobacterium bovis: a genomic and transcriptional approach, BP.DR
18/04609-3 - Comparative study of the infection dynamics of species of the Mycobacterium tuberculosis complex in human macrophages using RNA-Seq, BP.DD

Abstract

Tuberculosis (TB), the second leading human mortality cause by an infectious agent in the world, is caused by the Mycobacterium tuberculosis complex (MTBC), a zoonotic group of 12 genetically similar bacterial species from which the main human pathogens are: M. tuberculosis (the main causative agent of the disease), M. africanum 1 e 2, M. canettii, M. bovis e M. caprae. With the exception of M. canettii, all species clonally evolved from a M. tuberculosis-like ancestor through nucleotide deletions and mutations, resulting in variable phenotypes of host tropism and virulence. The three first species are highly adapted to human beings, while M. bovis and M. caprae have a wide host tropism with variable populational persistence. Compared to M. tuberculosis, M. africanum has a lower ability to progress to clinical disease and is restricted to West Africa, while M. canettii causes a rare, non-contagious form of TB and is restricted to the Horn of Africa. Thefore, the aim of this proposal is to compare the infection dynamics of these pathogens in their target cell, the human macrophage, associating data from transcriptomics that can provide evidence about the effect of genetic variability on MTBC phenotypes. Our hypotheses are: (i) members of MTBC have different global transcriptional, metabolic and cytosolic access profiles during infection of human macrophages and (ii) human macrophages infected with members of MTBC have different transcriptional, cytokine expression, cell death and phagosome maturation profiles. Thus, instead of directly evaluating M. tuberculosis pathogenicity onto cells, we will understand how evolution shaped MTBC as to present different phenotypes, focusing on the comparative analysis of members of this complex. It is expected that results from this study will aid in future identification of gene targets for therapeutics and bacterial mutant development for vaccines. (AU)

Distribution map of accesses to this page
Click here to view the access summary to this page.