Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactone
Mycobacterium ulcerans is the causal agent of Buruli ulcer, a chronic infectious disease and the third most common mycobacterial disease worldwide. Without early treatment, M. ulcerans provokes massive skin ulcers, caused by the mycolactone toxin, its main virulence factor. However, spontaneous heal...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-12-01
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| Series: | Virulence |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21505594.2021.1929749 |
| _version_ | 1828125689119768576 |
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| author | Marie Robbe-Saule Mélanie Foulon Isabelle Poncin Lucille Esnault Hugo Varet Rachel Legendre Alban Besnard Anna E. Grzegorzewicz Mary Jackson Stéphane Canaan Laurent Marsollier Estelle Marion |
| author_facet | Marie Robbe-Saule Mélanie Foulon Isabelle Poncin Lucille Esnault Hugo Varet Rachel Legendre Alban Besnard Anna E. Grzegorzewicz Mary Jackson Stéphane Canaan Laurent Marsollier Estelle Marion |
| author_sort | Marie Robbe-Saule |
| collection | DOAJ |
| description | Mycobacterium ulcerans is the causal agent of Buruli ulcer, a chronic infectious disease and the third most common mycobacterial disease worldwide. Without early treatment, M. ulcerans provokes massive skin ulcers, caused by the mycolactone toxin, its main virulence factor. However, spontaneous healing may occur in Buruli ulcer patients several months or years after the disease onset. We have shown, in an original mouse model, that bacterial load remains high and viable in spontaneously healed tissues, with a switch of M. ulcerans to low levels of mycolactone production, adapting its strategy to survive in such a hostile environment. This original model offers the possibility to investigate the regulation of mycolactone production, by using an RNA-seq strategy to study bacterial adaptation during mouse infection. Pathway analysis and characterization of the tissue environment showed that the bacillus adapted to its new environment by modifying its metabolic activity and switching nutrient sources. Thus, M. ulcerans ensures its survival in healing tissues by reducing its secondary metabolism, leading to an inhibition of mycolactone synthesis. These findings shed new light on mycolactone regulation and pave the way for new therapeutic strategies. |
| first_indexed | 2024-04-11T15:24:22Z |
| format | Article |
| id | doaj.art-1cb69814d64d40b389c32a0800f06a86 |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-04-11T15:24:22Z |
| publishDate | 2021-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-1cb69814d64d40b389c32a0800f06a862022-12-22T04:16:18ZengTaylor & Francis GroupVirulence2150-55942150-56082021-12-011211438145110.1080/21505594.2021.19297491929749Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactoneMarie Robbe-Saule0Mélanie Foulon1Isabelle Poncin2Lucille Esnault3Hugo Varet4Rachel Legendre5Alban Besnard6Anna E. Grzegorzewicz7Mary Jackson8Stéphane Canaan9Laurent Marsollier10Estelle Marion11Univ Angers, Inserm, CRCINAUniv Angers, Inserm, CRCINAAix-Marseille Université, CNRS, LISMUniv Angers, Inserm, CRCINACentre De Ressources Et Recherches Technologiques (C2RT), Institut PasteurCentre De Ressources Et Recherches Technologiques (C2RT), Institut PasteurUniv Angers, Inserm, CRCINAImmunology and Pathology, Colorado State UniversityImmunology and Pathology, Colorado State UniversityAix-Marseille Université, CNRS, LISMUniv Angers, Inserm, CRCINAUniv Angers, Inserm, CRCINAMycobacterium ulcerans is the causal agent of Buruli ulcer, a chronic infectious disease and the third most common mycobacterial disease worldwide. Without early treatment, M. ulcerans provokes massive skin ulcers, caused by the mycolactone toxin, its main virulence factor. However, spontaneous healing may occur in Buruli ulcer patients several months or years after the disease onset. We have shown, in an original mouse model, that bacterial load remains high and viable in spontaneously healed tissues, with a switch of M. ulcerans to low levels of mycolactone production, adapting its strategy to survive in such a hostile environment. This original model offers the possibility to investigate the regulation of mycolactone production, by using an RNA-seq strategy to study bacterial adaptation during mouse infection. Pathway analysis and characterization of the tissue environment showed that the bacillus adapted to its new environment by modifying its metabolic activity and switching nutrient sources. Thus, M. ulcerans ensures its survival in healing tissues by reducing its secondary metabolism, leading to an inhibition of mycolactone synthesis. These findings shed new light on mycolactone regulation and pave the way for new therapeutic strategies.http://dx.doi.org/10.1080/21505594.2021.1929749mycobacterium ulceranshost-bacterium interactionmycolactonerna-sequencingmetabolism |
| spellingShingle | Marie Robbe-Saule Mélanie Foulon Isabelle Poncin Lucille Esnault Hugo Varet Rachel Legendre Alban Besnard Anna E. Grzegorzewicz Mary Jackson Stéphane Canaan Laurent Marsollier Estelle Marion Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactone Virulence mycobacterium ulcerans host-bacterium interaction mycolactone rna-sequencing metabolism |
| title | Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactone |
| title_full | Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactone |
| title_fullStr | Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactone |
| title_full_unstemmed | Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactone |
| title_short | Transcriptional adaptation of Mycobacterium ulcerans in an original mouse model: New insights into the regulation of mycolactone |
| title_sort | transcriptional adaptation of mycobacterium ulcerans in an original mouse model new insights into the regulation of mycolactone |
| topic | mycobacterium ulcerans host-bacterium interaction mycolactone rna-sequencing metabolism |
| url | http://dx.doi.org/10.1080/21505594.2021.1929749 |
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