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17 results on '"Cioetto-Mazzabò, Laura"'

1. Implementing best practices on data generation and reporting of Mycobacterium tuberculosis in vitro assays within the ERA4TB consortium

Author

van Wijk, Rob C., Lucía, Ainhoa, Sudhakar, Pavan Kumar, Sonnenkalb, Lindsay, Gaudin, Cyril, Hoffmann, Eik, Dremierre, Bérénice, Aguilar-Ayala, Diana Angélica, Molin, Michael Dal, Rybniker, Jan, de Giorgi, Stefano, Cioetto-Mazzabò, Laura, Segafreddo, Greta, Manganelli, Riccardo, Degiacomi, Giulia, Recchia, Deborah, Pasca, Maria Rosalia, Simonsson, Ulrika S.H., and Ramón-García, Santiago

Published
2023
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3. Structure of the SigE regulatory network in Mycobacterium tuberculosis.

Author

Cioetto-Mazzabò, Laura, Sorze, Davide, Babic, Fedora, Boldrin, Francesca, Segafreddo, Greta, Provvedi, Roberta, and Manganelli, Riccardo

Subjects
MYCOBACTERIUM tuberculosis, BACK up systems, SIGMA receptors, GENETIC transcription, POLYMER networks, GENETIC regulation
Abstract

SigE is one of the main regulators of mycobacterial stress response and is characterized by a complex regulatory network based on two pathways, which have been partially characterized in conditions of surface stress. The first pathway is based on the induction of sigE transcription by the two-component system MprAB, while the second is based on the degradation of SigE antisigma factor RseA by ClpC1P2, a protease whose structural genes are induced by ClgR. We characterized the dynamics of the SigE network activation in conditions of surface stress and low pH in Mycobacterium tuberculosis. Using a series of mutants in which the main regulatory nodes of the network have been inactivated, we could explore their hierarchy, and we determined that MprAB had a key role in the network activation in both stress conditions through the induction of sigE. However, while in conditions of surface stress the absence of MprAB totally abrogated sigE induction, under low pH conditions it only resulted in a small delay of the induction of sigE. In this case, sigE induction was due to SigH, which acted as a MprAB backup system. The ClgR pathway, leading to the degradation of the SigE anti-sigma factor RseA, was shown to be essential for the activation of the SigE network only following surface stress, where it showed an equal hierarchy with the MprAB pathway. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Role of the Extracytoplasmic Function Sigma Factor SigE in the Stringent Response of Mycobacterium tuberculosis

Author

Baruzzo, Giacomo, primary, Serafini, Agnese, additional, Finotello, Francesca, additional, Sanavia, Tiziana, additional, Cioetto-Mazzabò, Laura, additional, Boldrin, Francesca, additional, Lavezzo, Enrico, additional, Barzon, Luisa, additional, Toppo, Stefano, additional, Provvedi, Roberta, additional, Manganelli, Riccardo, additional, and Di Camillo, Barbara, additional

Published
2023
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8. SigE: A master regulator of Mycobacterium tuberculosis

Author

Manganelli, Riccardo, primary, Cioetto-Mazzabò, Laura, additional, Segafreddo, Greta, additional, Boldrin, Francesca, additional, Sorze, Davide, additional, Conflitti, Marta, additional, Serafini, Agnese, additional, and Provvedi, Roberta, additional

Published
2023
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9. SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression

Author

Cioetto-Mazzabò, Laura, primary, Boldrin, Francesca, additional, Beauvineau, Claire, additional, Speth, Martin, additional, Marina, Alberto, additional, Namouchi, Amine, additional, Segafreddo, Greta, additional, Cimino, Mena, additional, Favre-Rochex, Sandrine, additional, Balasingham, Seetha, additional, Trastoy, Beatriz, additional, Munier-Lehmann, Hélène, additional, Griffiths, Gareth, additional, Gicquel, Brigitte, additional, Guerin, Marcelo E, additional, Manganelli, Riccardo, additional, and Alonso-Rodríguez, Noelia, additional

Published
2022
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12. Implementing Best Practises on Data Generation and Reporting of Mycobacterium tuberculosis Time Kill Assays: A Case Study of Standardized Protocol Within the ERA4TB Consortium

Author

van Wijk, Rob C., primary, Lucía, Ainhoa, additional, Sudhakar, Pavan Kumar, additional, Sonnenkalb, Lindsay, additional, Gaudin, Cyril, additional, Hoffmann, Eik, additional, Dremierre, Bérénice, additional, Aguilar-Ayala, Diana Angélica, additional, Dal Molin, Michael, additional, Rybniker, Jan, additional, de Giorgi, Stefano, additional, Cioetto-Mazzabò, Laura, additional, Segafreddo, Greta, additional, Manganelli, Riccardo, additional, Degiacomi, Giulia, additional, Recchia, Deborah, additional, Pasca, Maria Rosalia, additional, Simonsson, Ulrika S. H., additional, and Ramón García, Santiago, additional

Published
2022
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13. The Phosphatidyl- myo -Inositol Dimannoside Acyltransferase PatA Is Essential for Mycobacterium tuberculosis Growth In Vitro and In Vivo

Author

Boldrin, Francesca, primary, Anso, Itxaso, additional, Alebouyeh, Sogol, additional, Sevilla, Iker A., additional, Geijo, Mariví, additional, Garrido, Joseba M., additional, Marina, Alberto, additional, Cioetto Mazzabò, Laura, additional, Segafreddo, Greta, additional, Guerin, Marcelo E., additional, Manganelli, Riccardo, additional, and Prados-Rosales, Rafael, additional

Published
2021
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15. Construction and Characterization of the Mycobacterium tuberculosis sigE fadD26 Unmarked Double Mutant as a Vaccine Candidate

Author

Hernandez-Pando, Rogelio, primary, Shin, Sung Jae, additional, Clark, Simon, additional, Casonato, Stefano, additional, Becerril-Zambrano, Martin, additional, Kim, Hongmin, additional, Boldrin, Francesca, additional, Mata-Espinoza, Dulce, additional, Provvedi, Roberta, additional, Arbues, Ainhoa, additional, Marquina-Castillo, Brenda, additional, Cioetto Mazzabò, Laura, additional, Barrios-Payan, Jorge, additional, Martin, Carlos, additional, Cho, Sang-Nae, additional, Williams, Ann, additional, and Manganelli, Riccardo, additional

Published
2019
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16. Construction and Characterization of the Mycobacterium tuberculosissigE fadD26Unmarked Double Mutant as a Vaccine Candidate

Author

Hernandez-Pando, Rogelio, Shin, Sung Jae, Clark, Simon, Casonato, Stefano, Becerril-Zambrano, Martin, Kim, Hongmin, Boldrin, Francesca, Mata-Espinoza, Dulce, Provvedi, Roberta, Arbues, Ainhoa, Marquina-Castillo, Brenda, Cioetto Mazzabò, Laura, Barrios-Payan, Jorge, Martin, Carlos, Cho, Sang-Nae, Williams, Ann, and Manganelli, Riccardo

Abstract

Despite the great increase in the understanding of the biology and pathogenesis of Mycobacterium tuberculosisachieved by the scientific community in recent decades, tuberculosis (TB) still represents one of the major threats to global human health.

Published
2019
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17. SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression.

Author

Cioetto-Mazzabò L, Boldrin F, Beauvineau C, Speth M, Marina A, Namouchi A, Segafreddo G, Cimino M, Favre-Rochex S, Balasingham S, Trastoy B, Munier-Lehmann H, Griffiths G, Gicquel B, Guerin ME, Manganelli R, and Alonso-Rodríguez N

Subjects
Bacterial Proteins genetics, Bacterial Proteins metabolism, Heat-Shock Response genetics, Promoter Regions, Genetic, Transcription, Genetic, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis metabolism, Prodrugs pharmacology, Anti-Bacterial Agents pharmacology
Abstract

The emergence of drug-resistant Mycobacterium tuberculosis strains highlights the need to discover anti-tuberculosis drugs with novel mechanisms of action. Here we discovered a mycobactericidal strategy based on the prodrug activation of selected chemical derivatives classified as nitronaphthofurans (nNFs) mediated by the coordinated action of the sigH and mrx2 genes. The transcription factor SigH is a key regulator of an extensive transcriptional network that responds to oxidative, nitrosative, and heat stresses in M. tuberculosis. The nNF action induced the SigH stress response which in turn induced the mrx2 overexpression. The nitroreductase Mrx2 was found to activate nNF prodrugs, killing replicating, non-replicating and intracellular forms of M. tuberculosis. Analysis of SigH DNA sequences obtained from spontaneous nNF-resistant M. tuberculosis mutants suggests disruption of SigH binding to the mrx2 promoter site and/or RNA polymerase core, likely promoting the observed loss of transcriptional control over Mrx2. Mutations found in mrx2 lead to structural defects in the thioredoxin fold of the Mrx2 protein, significantly impairing the activity of the Mrx2 enzyme against nNFs. Altogether, our work brings out the SigH/Mrx2 stress response pathway as a promising target for future drug discovery programs., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2023
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