The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion
Abstract Bovine tuberculosis is a chronic consumptive zoonosis, causing significant economic losses and critical public health risks. Coronin-1A is a host cytoskeleton-associated protein that is crucial for understanding the inhibition of phagosome-lysosome fusion by Mycobacterium tuberculosis (M.tb...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Veterinary Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13567-025-01471-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861735453360128 |
|---|---|
| author | Jing Yang Zhunan Li Aicong Li Yayi Liu Xinyan Zhang Yong Zhang Yuanpeng Gao |
| author_facet | Jing Yang Zhunan Li Aicong Li Yayi Liu Xinyan Zhang Yong Zhang Yuanpeng Gao |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | Abstract Bovine tuberculosis is a chronic consumptive zoonosis, causing significant economic losses and critical public health risks. Coronin-1A is a host cytoskeleton-associated protein that is crucial for understanding the inhibition of phagosome-lysosome fusion by Mycobacterium tuberculosis (M.tb) to evade host innate immune clearance. However, the involvement of bovine Coronin-1A (bCoronin-1A) in M.tb infection and whether it can be manipulated so as to enhance host resistance against bovine tuberculosis remains to be seen. Here, we explored the role of bCoronin-1A in phagosome-lysosome fusion in M.tb-infected macrophages. We found that bCoronin-1A was upregulated at both the transcriptional and protein levels following M.tb infection of embryonic bovine lung (EBL) cells. Notably, bCoronin-1A was recruited to M.tb-containing phagosomes where it hindered phagosome-lysosome fusion, leading to increased intracellular mycobacterial survival. Further investigation revealed that mycobacterial lipoamide dehydrogenase C (LpdC) interacted with a single tryptophan-aspartate (WD) unit within the WD repeat domain of bCoronin-1A to sequester it on the phagosomes. The WD repeat domain mediated a decrease in intracellular calcium levels, which reduced levels of calmodulin-dependent kinase II (CaMKII) and its activated forms, thereby inhibiting lysosomal delivery. Overall, our findings revealed that bCoronin-1A had a critical impact on mycobacterial survival in macrophages by inhibiting calcium-mediated phagosome-lysosome fusion. This suggests that targeting bCoronin-1A as a key factor influencing mycobacterial survival may be an effective breeding strategy to develop tuberculosis-resistant dairy cows. |
| format | Article |
| id | doaj-art-82f01bbc6dea46fdaaa69ee78cfd10a3 |
| institution | Kabale University |
| issn | 1297-9716 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj-art-82f01bbc6dea46fdaaa69ee78cfd10a32025-02-09T12:50:05ZengBMCVeterinary Research1297-97162025-02-0156111410.1186/s13567-025-01471-6The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusionJing Yang0Zhunan Li1Aicong Li2Yayi Liu3Xinyan Zhang4Yong Zhang5Yuanpeng Gao6Key Laboratory of Livestock Biology, Northwest A&F UniversityKey Laboratory of Livestock Biology, Northwest A&F UniversityKey Laboratory of Livestock Biology, Northwest A&F UniversityKey Laboratory of Livestock Biology, Northwest A&F UniversityKey Laboratory of Livestock Biology, Northwest A&F UniversityKey Laboratory of Livestock Biology, Northwest A&F UniversityKey Laboratory of Livestock Biology, Northwest A&F UniversityAbstract Bovine tuberculosis is a chronic consumptive zoonosis, causing significant economic losses and critical public health risks. Coronin-1A is a host cytoskeleton-associated protein that is crucial for understanding the inhibition of phagosome-lysosome fusion by Mycobacterium tuberculosis (M.tb) to evade host innate immune clearance. However, the involvement of bovine Coronin-1A (bCoronin-1A) in M.tb infection and whether it can be manipulated so as to enhance host resistance against bovine tuberculosis remains to be seen. Here, we explored the role of bCoronin-1A in phagosome-lysosome fusion in M.tb-infected macrophages. We found that bCoronin-1A was upregulated at both the transcriptional and protein levels following M.tb infection of embryonic bovine lung (EBL) cells. Notably, bCoronin-1A was recruited to M.tb-containing phagosomes where it hindered phagosome-lysosome fusion, leading to increased intracellular mycobacterial survival. Further investigation revealed that mycobacterial lipoamide dehydrogenase C (LpdC) interacted with a single tryptophan-aspartate (WD) unit within the WD repeat domain of bCoronin-1A to sequester it on the phagosomes. The WD repeat domain mediated a decrease in intracellular calcium levels, which reduced levels of calmodulin-dependent kinase II (CaMKII) and its activated forms, thereby inhibiting lysosomal delivery. Overall, our findings revealed that bCoronin-1A had a critical impact on mycobacterial survival in macrophages by inhibiting calcium-mediated phagosome-lysosome fusion. This suggests that targeting bCoronin-1A as a key factor influencing mycobacterial survival may be an effective breeding strategy to develop tuberculosis-resistant dairy cows.https://doi.org/10.1186/s13567-025-01471-6Mycobacterium tuberculosisbovine Coronin-1AWD repeat domainphagosome-lysosome fusion |
| spellingShingle | Jing Yang Zhunan Li Aicong Li Yayi Liu Xinyan Zhang Yong Zhang Yuanpeng Gao The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion Veterinary Research Mycobacterium tuberculosis bovine Coronin-1A WD repeat domain phagosome-lysosome fusion |
| title | The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion |
| title_full | The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion |
| title_fullStr | The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion |
| title_full_unstemmed | The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion |
| title_short | The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion |
| title_sort | tryptophan aspartate wd repeat domain of bovine coronin 1a promotes mycobacterial survival by inhibiting calcium signaling mediated phagosome lysosome fusion |
| topic | Mycobacterium tuberculosis bovine Coronin-1A WD repeat domain phagosome-lysosome fusion |
| url | https://doi.org/10.1186/s13567-025-01471-6 |
| work_keys_str_mv | AT jingyang thetryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT zhunanli thetryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT aicongli thetryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT yayiliu thetryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT xinyanzhang thetryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT yongzhang thetryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT yuanpenggao thetryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT jingyang tryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT zhunanli tryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT aicongli tryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT yayiliu tryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT xinyanzhang tryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT yongzhang tryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion AT yuanpenggao tryptophanaspartatewdrepeatdomainofbovinecoronin1apromotesmycobacterialsurvivalbyinhibitingcalciumsignalingmediatedphagosomelysosomefusion |