Impact of Genomic Deletion RD16 on the Expression of the <i>Mycobacterium bovis</i> BCG Moreau VapBC47 Toxin-Antitoxin System
<i>Mycobacterium bovis</i> BCG is the only vaccine against tuberculosis. The variable forms of cultivation throughout the years, before seed-lots were developed, allowed in vitro evolution of the original strain, generating a family of vaccines with different phenotypic and genotypic cha...
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MDPI AG
2023-08-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/8/412 |
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| author | Talita Duarte Pagani Paloma Rezende Corrêa Cristiane Lima Leonardo Henrique Ferreira Gomes Marcos Gustavo Araujo Schwarz Teca Calcagno Galvão Wim Maurits Degrave Napoleão Fonseca Valadares Leila Mendonça-Lima |
| author_facet | Talita Duarte Pagani Paloma Rezende Corrêa Cristiane Lima Leonardo Henrique Ferreira Gomes Marcos Gustavo Araujo Schwarz Teca Calcagno Galvão Wim Maurits Degrave Napoleão Fonseca Valadares Leila Mendonça-Lima |
| author_sort | Talita Duarte Pagani |
| collection | DOAJ |
| description | <i>Mycobacterium bovis</i> BCG is the only vaccine against tuberculosis. The variable forms of cultivation throughout the years, before seed-lots were developed, allowed in vitro evolution of the original strain, generating a family of vaccines with different phenotypic and genotypic characteristics. Molecular studies revealed regions of difference (RDs) in the genomes of the various BCG strains. This work aims to characterize the gene pair <i>rv3407-rv3408</i> (<i>vapB47</i>-<i>vapC47</i>), coding for a toxin–antitoxin system of the VapBC family, and to evaluate possible transcriptional effects due to the adjacent BCG Moreau-specific genomic deletion RD16. We show that these genes are co-transcribed in BCG strains Moreau and Pasteur, and that the inactivation of an upstream transcriptional repressor (Rv3405c) due to RD16 has a polar effect, leading to increased <i>vapBC47</i> expression. Furthermore, we detect VapB47 DNA binding in vitro, dependent on a 5′ <i>vapB47</i> sequence that contributes to a palindrome, spanning the promoter and coding region. Our data shed light on the regulation of VapBC systems and on the impact of the BCG Moreau RD16 deletion in the expression of adjacent genes, contributing to a better understanding of BCG Moreau physiology. |
| first_indexed | 2024-03-11T00:02:52Z |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-11T00:02:52Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-ecaf66e95a7447b28c50f39d0a5f6e6b2023-11-19T00:41:50ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-08-014586538654910.3390/cimb45080412Impact of Genomic Deletion RD16 on the Expression of the <i>Mycobacterium bovis</i> BCG Moreau VapBC47 Toxin-Antitoxin SystemTalita Duarte Pagani0Paloma Rezende Corrêa1Cristiane Lima2Leonardo Henrique Ferreira Gomes3Marcos Gustavo Araujo Schwarz4Teca Calcagno Galvão5Wim Maurits Degrave6Napoleão Fonseca Valadares7Leila Mendonça-Lima8Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, BrazilLaboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, BrazilLaboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, BrazilLaboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, BrazilLaboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, BrazilLaboratório de Bacteriologia, Centro de Referência Prof. Hélio Fraga, Escola Nacional de Saúde Pública Sergio Arouca, Fiocruz, Rio de Janeiro 21041-210, RJ, BrazilLaboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, BrazilDepartamento de Biologia Celular, Universidade de Brasília, Brasília 70904-970, DF, BrazilLaboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil<i>Mycobacterium bovis</i> BCG is the only vaccine against tuberculosis. The variable forms of cultivation throughout the years, before seed-lots were developed, allowed in vitro evolution of the original strain, generating a family of vaccines with different phenotypic and genotypic characteristics. Molecular studies revealed regions of difference (RDs) in the genomes of the various BCG strains. This work aims to characterize the gene pair <i>rv3407-rv3408</i> (<i>vapB47</i>-<i>vapC47</i>), coding for a toxin–antitoxin system of the VapBC family, and to evaluate possible transcriptional effects due to the adjacent BCG Moreau-specific genomic deletion RD16. We show that these genes are co-transcribed in BCG strains Moreau and Pasteur, and that the inactivation of an upstream transcriptional repressor (Rv3405c) due to RD16 has a polar effect, leading to increased <i>vapBC47</i> expression. Furthermore, we detect VapB47 DNA binding in vitro, dependent on a 5′ <i>vapB47</i> sequence that contributes to a palindrome, spanning the promoter and coding region. Our data shed light on the regulation of VapBC systems and on the impact of the BCG Moreau RD16 deletion in the expression of adjacent genes, contributing to a better understanding of BCG Moreau physiology.https://www.mdpi.com/1467-3045/45/8/412<i>Mycobacterium bovis</i> BCG Moreau<i>Mycobacterium tuberculosis</i>toxin–antitoxin systemVapBC47BCG vaccine |
| spellingShingle | Talita Duarte Pagani Paloma Rezende Corrêa Cristiane Lima Leonardo Henrique Ferreira Gomes Marcos Gustavo Araujo Schwarz Teca Calcagno Galvão Wim Maurits Degrave Napoleão Fonseca Valadares Leila Mendonça-Lima Impact of Genomic Deletion RD16 on the Expression of the <i>Mycobacterium bovis</i> BCG Moreau VapBC47 Toxin-Antitoxin System Current Issues in Molecular Biology <i>Mycobacterium bovis</i> BCG Moreau <i>Mycobacterium tuberculosis</i> toxin–antitoxin system VapBC47 BCG vaccine |
| title | Impact of Genomic Deletion RD16 on the Expression of the <i>Mycobacterium bovis</i> BCG Moreau VapBC47 Toxin-Antitoxin System |
| title_full | Impact of Genomic Deletion RD16 on the Expression of the <i>Mycobacterium bovis</i> BCG Moreau VapBC47 Toxin-Antitoxin System |
| title_fullStr | Impact of Genomic Deletion RD16 on the Expression of the <i>Mycobacterium bovis</i> BCG Moreau VapBC47 Toxin-Antitoxin System |
| title_full_unstemmed | Impact of Genomic Deletion RD16 on the Expression of the <i>Mycobacterium bovis</i> BCG Moreau VapBC47 Toxin-Antitoxin System |
| title_short | Impact of Genomic Deletion RD16 on the Expression of the <i>Mycobacterium bovis</i> BCG Moreau VapBC47 Toxin-Antitoxin System |
| title_sort | impact of genomic deletion rd16 on the expression of the i mycobacterium bovis i bcg moreau vapbc47 toxin antitoxin system |
| topic | <i>Mycobacterium bovis</i> BCG Moreau <i>Mycobacterium tuberculosis</i> toxin–antitoxin system VapBC47 BCG vaccine |
| url | https://www.mdpi.com/1467-3045/45/8/412 |
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