| Author | Schwarz, Marcos Gustavo Araujo | |
| Author | Antunes, Deborah | |
| Author | Corrêa, Paloma Rezende | |
| Author | Gonçalves, Antonio José da Silva | |
| Author | Malaga, Wladimir | |
| Author | Caffarena, Ernesto Raul | |
| Author | Guilhot, Christophe | |
| Author | Lima, Leila Mendonça | |
| Access date | 2021-04-11T13:35:12Z | |
| Available date | 2021-04-11T13:35:12Z | |
| Document date | 2021 | |
| Citation | SCHWARZ, Marcos Gustavo Araujo et al. Mycobacterium tuberculosis and M. bovis BCG Moreau Fumarate Reductase Operons Produce Different Polypeptides That May Be Related to Non-canonical Functions. Frontiers in Microbiology, v. 11, Article 624121, p. 1-15, Jan. 2021. | pt_BR |
| ISSN | 1664-302X | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/46626 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Mycobacterium bovis BCG Moreau | pt_BR |
| Subject in Portuguese | Fumarato redutase | pt_BR |
| Subject in Portuguese | Sequência homopolimérica | pt_BR |
| Subject in Portuguese | Deslizamento transcricional | pt_BR |
| Subject in Portuguese | Vacina contra Tuberculose | pt_BR |
| Title | Mycobacterium tuberculosis and M. bovis BCG Moreau Fumarate Reductase Operons Produce Different Polypeptides That May Be Related to Non-canonical Functions | pt_BR |
| Type | Article | |
| DOI | 10.3389/fmicb.2020.624121 | |
| Abstract | Tuberculosis is a world widespread disease, caused by Mycobacterium tuberculosis
(M.tb). Although considered an obligate aerobe, this organism can resist life-limiting
conditions such as microaerophily mainly due to its set of enzymes responsible
for energy production and coenzyme restoration under these conditions. One of
these enzymes is fumarate reductase, an heterotetrameric complex composed of
a catalytic (FrdA), an iron-sulfur cluster (FrdB) and two transmembrane (FrdC and
FrdD) subunits involved in anaerobic respiration and important for the maintenance of
membrane potential. In this work, aiming to further characterize this enzyme function
in mycobacteria, we analyzed the expression of FrdB-containing proteins in M.tb and
Mycobacterium bovis Bacillus Calmette–Guérin (BCG) Moreau, the Brazilian vaccine
strain against tuberculosis. We identified three isoforms in both mycobacteria, two of
them corresponding to the predicted encoded polypeptides of M.tb (27 kDa) and BCG
Moreau (40 kDa) frd sequences, as due to an insertion on the latter’s operon a fused
FrdBC protein is expected. The third 52 kDa band can be explained by a transcriptional
slippage event, typically occurring when mutation arises in a repetitive region within a
coding sequence, thought to reduce its impact allowing the production of both native
and variant forms. Comparative modeling of the M.tb and BCG Moreau predicted
protein complexes allowed the detection of subtle overall differences, showing a high
degree of structure and maybe functional resemblance among them. Axenic growth and
macrophage infection assays show that the frd locus is important for proper bacterial
development in both scenarios, and that both M.tb’s and BCG Moreau’s alleles can
partially revert the hampered phenotype of the knockout strain. Altogether, our results
show that the frdABCD operon of Mycobacteria may have evolved to possess other yet
non-described functions, such as those necessary during aerobic logarithmic growth
and early stage steps of infection. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier. Toulouse, France. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Grupo de Biofísica Computacional e Modelagem Molécula. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier. Toulouse, France. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Fumarate reductase | pt_BR |
| Subject | Mycobacterium bovis BCG Moreau | pt_BR |
| Subject | Homopolymeric sequence | pt_BR |
| Subject | Transcriptional slippage | pt_BR |
| Subject | Tuberculosis vaccine | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
