1. The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion
- Author
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Jing Yang, Zhunan Li, Aicong Li, Yayi Liu, Xinyan Zhang, Yong Zhang, and Yuanpeng Gao
- Subjects
Mycobacterium tuberculosis ,bovine Coronin-1A ,WD repeat domain ,phagosome-lysosome fusion ,Veterinary medicine ,SF600-1100 - Abstract
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.
- Published
- 2025
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