Host adaption of Mycobacterium tuberculosis and Mycobacterium bovis: a genomic and transcriptional approach

• Grant number: 17/04617-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2018
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Ana Marcia de Sá Guimarães
• Grantee: Cristina Kraemer Zimpel
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/26108-0 - Systems and comparative biology of Mycobacterium tuberculosis complex: effects of genetic variability on bacterial phenotype, AP.JP
• Associated scholarship(s): 19/10896-8 - Transcriptomic and metabolic features of Mycobacterium tuberculosis and Mycobacterium bovis during human macrophage infection, BE.EP.DR

Abstract

Tuberculosis is caused by members of the Mycobacterium Tuberculosis Complex (MTBC), a bacterial group that comprises twelve pathogen species that infect human beings and/or animals. The most frequent causative species of the disease are M. tuberculosis and M. bovis. Members of this complex evolved clonally from a M. tuberculosis ancestor and have high genomic identity, differing only by Single Nucleotide Polymorphisms (SNPs) and regions of difference (indels, RDs). Despite this high genetic similarity, MTBC members demonstrate phenotypic variations related to virulence and host tropism. While M. tuberculosis is highly adapted to human beings (i.e. a specialist bacterium) and is the major causative agent of the disease in this population, M. bovis shows unrestricted host predilection (i.e. a generalist bacterium), and can affect several animal species, including human beings, but with variable populational persistence. Although several reservoir animal species have been described for M. bovis, this pathogen does not persist in the human population; M. bovis transmission among patients is considered rare, even in cases of pulmonary disease. Therefore, in order to explain the unrestricted host preference of M. bovis and why this pathogen does not persist in the human population, this project aims (i) to sequence and annotate the genomes of M. bovis isolated from different non-bovine species and to compare to M. bovis genomes isolated from bovines and strains of M. tuberculosis, and (ii) to compare the global transcriptional profiles of M. bovis and M. tuberculosis during human macrophage infections and identify their activated metabolic pathways using Flux Balance Analysis (FBA). The comparative analysis to be performed herein will help elucidate the host-pathogen interaction of M. bovis and M. tuberculosis, and to identify genes related to macrophage infection that may serve as targets for treatment protocols and vaccine development. (AU)

Scientific publications

(5)

(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)

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)

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)

LIMA, DAIANE A. R.; ZIMPEL, CRISTINA K.; PATANE, JOSE S.; SILVA-PEREIRA, TAIANA TAINA; ETGES, RODRIGO N.; RODRIGUES, RUDIELLE A.; DAVILA, ALBERTO M. R.; IKUTA, CASSIA Y.; NETO, JOSE S. FERREIRA; GUIMARAES, ANA MARCIA S.; et al. Genomic analysis of an outbreak of bovine tuberculosis in a man-made multi-host species system: A call for action on wildlife in Brazil. TRANSBOUNDARY AND EMERGING DISEASES, OCT 2021. (17/04617-3, 19/10896-8)

SILVA-PEREIRA, TAIANA T.; IKUTA, CASSIA Y.; ZIMPEL, CRISTINA K.; CAMARGO, NAILA C. S.; DE SOUZA FILHO, ANTONIO F.; FERREIRA NETO, JOSE S.; HEINEMANN, MARCOS B.; GUIMARAES, ANA M. S.. Genome sequencing of Mycobacterium pinnipedii strains: genetic characterization and evidence of superinfection in a South American sea lion (Otaria flavescens). BMC Genomics, v. 20, n. 1, DEC 30 2019. (17/04617-3, 17/20147-7)

ZIMPEL, CRISTINA KRAEMER; PATANE, JOSE SALVATORE L.; PROENGA GUEDES, AURELIANO COELHO; DE SOUZA, ROBSON F.; SILVA-PEREIRA, TAIANA T.; SOLER CAMARGO, NAILA C.; DE SOUZA FILHO, ANTONIO F.; IKUTA, CASSIA Y.; FERREIRA NETO, JOSE SOARES; SETUBAL, JOAO CARLOS; et al. Global Distribution and Evolution of Mycobacterium bovis Lineages. FRONTIERS IN MICROBIOLOGY, v. 11, MAY 7 2020. (17/04617-3, 17/20147-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ZIMPEL, Cristina Kraemer. Host adaptation of Mycobacterium tuberculosis and Mycobacterium bovis: a genomic and transcriptional approach. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) São Paulo.