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

• Grant number: 16/26108-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: December 01, 2017
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Ana Marcia de Sá Guimarães
• Grantee: Ana Marcia de Sá Guimarães
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Lucas Miranda Marques ; Maria Regina D'Império Lima
• Associated research grant(s): 20/07251-2 - Evaluation of Syrian hamsters (Mesocricetus auratus) as model of infection and disease by SARS-CoV-2, AP.R
• Associated scholarship(s): 22/16602-9 - Survival and tolerance of Mycobacterium africanum L5 and L6 to copper., BP.TT; 22/16769-0 - Survival and tolerance to zinc as determinants of the control of phagosome acidification by bacteria of the Mycobacterium tuberculosis complex, BP.TT; 23/00609-7 - Training in good practices of biosafety level 3 laboratories, BP.TT; + associated scholarships 21/02736-0 - Good practices and operation of biosafety level 3+ laboratories, BP.TT; 20/13179-2 - Evaluation of the cytosol escape of actinobacteria from the phagosome of human macrophages, BP.IC; 19/21847-8 - Comparative study of the immune response of human macrophages infected with different strains of the Mycobacterium tuberculosis complex, BP.MS; 19/20786-5 - Improvement in good practices and operation of level 3+ biosafety laboratories, BP.TT; 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 - associated scholarships

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)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GUIMARAES, ANA M. S.; ZIMPEL, CRISTINA K.. Mycobacterium bovis: From Genotyping to Genome Sequencing. MICROORGANISMS, v. 8, n. 5, MAY 2020. (16/26108-0, 17/04617-3)

CARNEIRO, PAULO ALEX; ZIMPEL, CRISTINA KRAEMER; PASQUATTI, TAYNARA NUNES; SILVA-PEREIRA, TAIANA T.; TAKATANI, HARUO; SILVA, CHRISTIAN B. D. G.; ABRAMOVITCH, ROBERT B.; SA GUIMARAES, ANA MARCIA; DAVILA, ALBERTO M. R.; ARAUJO, FLABIO R.; et al. Genetic Diversity and Potential Paths of Transmission of Mycobacterium bovis in the Amazon: The Discovery of M. bovis Lineage Lb1 Circulating in South America. FRONTIERS IN VETERINARY SCIENCE, v. 8, FEB 16 2021. (16/26108-0, 19/10896-8, 17/04617-3)

DE MORAIS, HELIO AUTRAN; DOS SANTOS, ANDREA PIRES; DO NASCIMENTO, NAILA CANNES; KMETIUK, LOUISE BACH; BARBOSA, DAVID SOEIRO; BRANDAO, PAULO EDUARDO; GUIMARAES, ANA MARCIA SA; PETTAN-BREWER, CHRISTINA; BIONDO, ALEXANDER WELKER. Natural Infection by SARS-CoV-2 in Companion Animals: A Review of Case Reports and Current Evidence of Their Role in the Epidemiology of COVID-19. FRONTIERS IN VETERINARY SCIENCE, v. 7, OCT 27 2020. (16/26108-0, 20/07251-2)

GUIMARAES, ANA; ALLEN, ADRIAN R.; PRICE-CARTER, MARIAN L.. Editorial: Evolution and genomics of the Mycobacterium tuberculosis complex. FRONTIERS IN MICROBIOLOGY, v. 14, p. 3-pg., 2023-03-03. (16/26108-0)