Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity
Abstract Type VII secretion systems participate in protein export, virulence, conjugation, and metabolic regulation. Five subtypes (ESX-1 to ESX-5) exist, each with specific roles and well-characterized secretion profiles in various mycobacterial species. Mycobacterium abscessus, encodes only ESX-3...
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07572-4 |
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| author | Wassim Daher Vincent Le Moigne Yara Tasrini Shweta Parmar Danielle L. Sexton John Jairo Aguilera-Correa Valentin Berdal Elitza I. Tocheva Jean-Louis Herrmann Laurent Kremer |
| author_facet | Wassim Daher Vincent Le Moigne Yara Tasrini Shweta Parmar Danielle L. Sexton John Jairo Aguilera-Correa Valentin Berdal Elitza I. Tocheva Jean-Louis Herrmann Laurent Kremer |
| author_sort | Wassim Daher |
| collection | DOAJ |
| description | Abstract Type VII secretion systems participate in protein export, virulence, conjugation, and metabolic regulation. Five subtypes (ESX-1 to ESX-5) exist, each with specific roles and well-characterized secretion profiles in various mycobacterial species. Mycobacterium abscessus, encodes only ESX-3 and ESX-4. Here, single and double M. abscessus mutants lacking the main ATPases EccC3 and EccC4 were used to define ESX-3 and ESX-4 contributions to substrate secretion and virulence. Our results demonstrate that EsxG/H secretion depends entirely on ESX-3, whereas both ESX-3 and ESX-4 secrete EsxU/T. Furthermore, two newly identified PE/PPE substrates (MAB_0046/MAB_0047) require ESX-3 for secretion. Functional complementation restored secretion and revealed subpolar localization of these systems. Macrophage infections showed that ESX-3 and ESX-4 contribute to bacterial internalization, phagosomal escape, and intracellular survival. In mice, infections with eccC3- and/or eccC4-deletion mutants resulted in complete survival and reduced bacterial loads in the lungs. These findings demonstrate that both ESX systems drive M. abscessus pathogenicity. |
| format | Article |
| id | doaj-art-e6c2ea9a6ad2445296882e642337a095 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-e6c2ea9a6ad2445296882e642337a0952025-02-09T12:50:17ZengNature PortfolioCommunications Biology2399-36422025-02-018111510.1038/s42003-025-07572-4Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicityWassim Daher0Vincent Le Moigne1Yara Tasrini2Shweta Parmar3Danielle L. Sexton4John Jairo Aguilera-Correa5Valentin Berdal6Elitza I. Tocheva7Jean-Louis Herrmann8Laurent Kremer9Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, 1919 route de MendeUniversité Paris-Saclay, UVSQ, Inserm, Infection et inflammationCentre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, 1919 route de MendeDepartment of Microbiology and Immunology, University of British ColumbiaDepartment of Microbiology and Immunology, University of British ColumbiaCentre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, 1919 route de MendeCentre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, 1919 route de MendeDepartment of Microbiology and Immunology, University of British ColumbiaUniversité Paris-Saclay, UVSQ, Inserm, Infection et inflammationCentre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, 1919 route de MendeAbstract Type VII secretion systems participate in protein export, virulence, conjugation, and metabolic regulation. Five subtypes (ESX-1 to ESX-5) exist, each with specific roles and well-characterized secretion profiles in various mycobacterial species. Mycobacterium abscessus, encodes only ESX-3 and ESX-4. Here, single and double M. abscessus mutants lacking the main ATPases EccC3 and EccC4 were used to define ESX-3 and ESX-4 contributions to substrate secretion and virulence. Our results demonstrate that EsxG/H secretion depends entirely on ESX-3, whereas both ESX-3 and ESX-4 secrete EsxU/T. Furthermore, two newly identified PE/PPE substrates (MAB_0046/MAB_0047) require ESX-3 for secretion. Functional complementation restored secretion and revealed subpolar localization of these systems. Macrophage infections showed that ESX-3 and ESX-4 contribute to bacterial internalization, phagosomal escape, and intracellular survival. In mice, infections with eccC3- and/or eccC4-deletion mutants resulted in complete survival and reduced bacterial loads in the lungs. These findings demonstrate that both ESX systems drive M. abscessus pathogenicity.https://doi.org/10.1038/s42003-025-07572-4 |
| spellingShingle | Wassim Daher Vincent Le Moigne Yara Tasrini Shweta Parmar Danielle L. Sexton John Jairo Aguilera-Correa Valentin Berdal Elitza I. Tocheva Jean-Louis Herrmann Laurent Kremer Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity Communications Biology |
| title | Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity |
| title_full | Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity |
| title_fullStr | Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity |
| title_full_unstemmed | Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity |
| title_short | Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity |
| title_sort | deletion of esx 3 and esx 4 secretion systems in mycobacterium abscessus results in highly impaired pathogenicity |
| url | https://doi.org/10.1038/s42003-025-07572-4 |
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