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
  • 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. [email protected].
  • 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. [email protected].
  • 6. Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China. [email protected].
  • 7. College of Marine Sciences, University of Chinese Academy of Sciences, Qingdao, China. [email protected].
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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