The BCG Moreau RD16 deletion inactivates a repressor reshaping transcription of an adjacent gene

Galvão, Teca Calcagno; Lima, Cristiane R.; Gomes, Leonardo Henrique Ferreira; Pagani, Talita Duarte; Ferreira, Marcelo Alves; Gonçalves, Antonio S.; Corrêa, Paloma Rezende; Degrave, Wim; Mendonça-Lima, Leila

doi:10.1016/j.tube.2013.11.004

Cited by 16 publications

(17 citation statements)

References 41 publications

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“…Similarly there are deletions in TFTRs in other strains of M. bovis BCG that might influence the efficacy of the vaccine. Rv3405c is in the RD16 region deleted from M. bovis BCG Moreau but a link between this deletion and vaccine efficacy is unknown [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

et al. 2015

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BackgroundMycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria.ResultsWe used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs.ConclusionThis study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

et al. 2015

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“…Whole-genome sequencing revealed that all resistant Mtb isolates contained mutations in rv3405c, most of which were predicted to inactivate rv3405c; three strains harbored mutations only in rv3405c (table S1). Rv3405c is a transcriptional repressor that controls rv3406 in the Mycobacterium bovis Bacille Calmette-Guérin (BCG) strain (22). When we compared mRNAs from Bio-AMS-resistant Mtb isolates with those from wildtype Mtb, we detected a marked change in rv3406 (table S2), which resulted in overexpression of Rv3406 protein ( fig.…”

Section: Emergence Of Mtb Resistance To Chemical Bpl Inactivationmentioning

confidence: 99%

Targeting protein biotinylation enhances tuberculosis chemotherapy

et al. 2018

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“… 12 Previous studies by our group have established that Rv3405c is a transcriptional regulator that represses the expression of the adjacent rv3406 gene. 13 As a consequence, BCG Moreau accumulates Rv3406 due to its constitutive expression; in comparison, BCG Pasteur does not produce Rv3406 under the standard culture conditions. Complementation of BCG Moreau with a functional copy of rv3405c obtained from BCG Pasteur restores the regulation and abolishes the Rv3406 accumulation.…”

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confidence: 99%

“…Complementation of BCG Moreau with a functional copy of rv3405c obtained from BCG Pasteur restores the regulation and abolishes the Rv3406 accumulation. 13 …”

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confidence: 99%

“…The aim of the present study is to evaluate the functional impact of the loss of Rv3405c on the M. bovis BCG Moreau viability and its initial interaction with the host cells using a THP-1 cell model, monitoring the behaviour of the bacilli and the host cells in response to infection. Two BCG Moreau recombinant strains 13 were compared in this study: the first strain (M:: 05c ) harbours a functional copy of rv3405c from the BCG Pasteur cloned in the pUS972 plasmid, 16 and the second strain carries the empty vector (MD 05c ). Both strains were grown in the 7H9 medium supplemented with 10% ADC and 0.05% Tween-80 in the presence of 25 μg mL -1 kanamycin.…”

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Gain of function in Mycobacterium bovis BCG Moreau due to loss of a transcriptional repressor

Monteiro-Maia

Corrêa

Sousa-Vasconcelos

et al. 2018

Mem. Inst. Oswaldo Cruz

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The Bacille Calmette-Guérin (BCG) vaccine comprises a family of genetically different strains derived by the loss of genomic regions (RDs) and other mutations. In BCG Moreau, loss of RD16 inactivates rv3405c * , encoding a transcriptional repressor that negatively regulates the expression of Rv3406, an alkyl sulfatase. To evaluate the impact of this loss on the BCG and host cell viability and the cytokine profile, THP-1 cells were infected with BCG Moreau (harbouring the empty vector) and a complemented strain carrying a functional copy of rv3405c. Viability of the host cells and bacteria as well as the pattern of cytokine secretion were evaluated. Our results show that the viability of BCG Moreau is higher than that of the complemented strain in an axenic medium, suggesting a possible functional gain associated with the constitutive expression of Rv3406. Viability of the host cells did not vary significantly between recombinant strains, but differences in the profiles of the cytokine secretion (IL-1β and IL-6) were observed. Our results suggest an example of a functional gain due to gene loss contributing to the elucidation of the impact of RD16 on the physiology of BCG Moreau.

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The BCG Moreau RD16 deletion inactivates a repressor reshaping transcription of an adjacent gene

Cited by 16 publications

References 41 publications

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

Targeting protein biotinylation enhances tuberculosis chemotherapy

Gain of function in Mycobacterium bovis BCG Moreau due to loss of a transcriptional repressor

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