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Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
Bacterial CipB is an exogenous receptor to drive the mitophagy-TFEB axis and promote pathogenesis
Shuai Liu1,2, Lina Ma1, Ruiqi Lv1
1State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University , Wuhan, China.
Abstract:
Mitophagy transports mitochondria to lysosomes for degradation to maintain energy homeostasis, inflammation, and immunity. Here, we identify CipB, a type III secretion system (T3SS) effector from Chromobacterium violaceum, as a novel exogenous mitophagy receptor. CipB targets mitochondria by the mitochondrial protein TUFM and recruits autophagosomes via its LC3-interacting region (LIR) motifs. This process initiates the mitophagy-TFEB axis, triggering TFEB nuclear translocation and suppression of proinflammatory cytokines, thereby promoting bacterial survival and pathogenesis. CipB represents a conserved family of T3SS effectors employed by diverse pathogens to manipulate host mitophagy. Using a mouse model, CipB's mitophagy receptor function is critical for C. violaceum colonization in the liver and spleen, underscoring its role in bacterial virulence. This study reveals a novel mechanism by which bacterial pathogens exploit host mitophagy to suppress immune responses, defining CipB as a paradigm for exogenous mitophagy receptors. These findings advance our understanding of pathogen-host interactions and highlight the mitophagy-TFEB axis as a potential signaling pathway against bacterial infection.
Insights
This study identifies CipB, a bacterial protein, as a novel mitophagy receptor that helps pathogens evade immune responses. CipB manipulates host mitophagy to promote bacterial survival and virulence.
Area of Science:
- Cell Biology
- Microbiology
- Immunology
Background:
- Mitophagy is crucial for cellular homeostasis, regulating energy, inflammation, and immunity by degrading mitochondria.
- Pathogens often evolve mechanisms to subvert host cellular processes for their own benefit.
Purpose of the Study:
- To identify novel exogenous mitophagy receptors used by bacterial pathogens.
- To elucidate the mechanism by which bacterial effectors manipulate host mitophagy for pathogenesis.
Main Methods:
- Identification of CipB as a type III secretion system (T3SS) effector from Chromobacterium violaceum.
- Investigating CipB's interaction with mitochondrial protein TUFM and autophagosomes via LC3-interacting region (LIR) motifs.
- Utilizing a mouse model to assess the role of CipB in bacterial colonization and virulence.
Main Results:
- CipB functions as an exogenous mitophagy receptor, targeting mitochondria and initiating the mitophagy-TFEB pathway.
- CipB triggers TFEB nuclear translocation, suppresses proinflammatory cytokines, and promotes bacterial survival and pathogenesis.
- CipB's mitophagy receptor activity is essential for Chromobacterium violaceum colonization in mouse liver and spleen.
Conclusions:
- Bacterial pathogens can exploit host mitophagy via exogenous receptors like CipB to suppress immune responses.
- CipB represents a conserved family of T3SS effectors that manipulate host mitophagy, highlighting a novel virulence strategy.
- The mitophagy-TFEB axis is a potential target for therapeutic intervention against bacterial infections.
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