2. Academic Validation
  3. Bacillus cereus cereolysin O induces pyroptosis in an undecapeptide-dependent manner

Bacillus cereus cereolysin O induces pyroptosis in an undecapeptide-dependent manner

  • Cell Death Discov. 2024 Mar 8;10(1):122. doi: 10.1038/s41420-024-01887-7.
Yujian Wang 1 2,  Jingchang Luo 1 2 3,  Xiaolu Guan 1 2 3,  Yan Zhao 4,  Li Sun 5 6 7
Affiliations

Affiliations

  • 1 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China.
  • 2 Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China.
  • 3 College of Marine Sciences, University of Chinese Academy of Sciences, Qingdao, China.
  • 4 Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China. zhaoyan1316@163.com.
  • 5 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China. lsun@qdio.ac.cn.
  • 6 Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China. lsun@qdio.ac.cn.
  • 7 College of Marine Sciences, University of Chinese Academy of Sciences, Qingdao, China. lsun@qdio.ac.cn.
PMID: 38458999 DOI: 10.1038/s41420-024-01887-7
Abstract

Bacillus cereus is a clinically significant foodborne pathogen that causes severe gastrointestinal and non-gastrointestinal disease. Cereolysin O (CLO) is a putative virulence factor of B. cereus, and its function remains to be investigated. In this study, we examined the biological activity of CLO from a deep sea B. cereus isolate. CLO was highly toxic to mammalian cells and triggered Pyroptosis through NLRP3 inflammasome-mediated Caspase 1 and gasdermin D activation. CLO-induced cell death involved ROS accumulation and K+ efflux, and was blocked by serum lipids. CLO bound specifically to Cholesterol, and this binding was essential to CLO cytotoxicity. The structural integrity of the three tryptophan residues in the C-terminal undecapeptide was vital for CLO to interact with membrane lipids and cause membrane perforation. Taken together, these results provided new insights into the molecular mechanism of B. cereus CLO-mediated cytotoxicity.

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