Volume 31, No 8, Aug 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 8, August 2021: 935-938   |  Open Access

LETTERS TO THE EDITOR

Sulfated glycosaminoglycans and low-density lipoprotein receptor mediate the cellular entry of Clostridium novyi alpha-toxin

Yao Zhou^1,2,3 , Diyin Li^1,2,3 , Jianhua Luo^1,2,3 , Aizhong Chen^1,2,3 , Xingxing Li^1,2,3 , Zhenrui Pan^1,2,3 , Li Wan^1,2,3 , Liuqing He^1,2,3 , Danyang Li^1,2,3 , Yanyan Li^1,2,3 , Min Dong^4,5 , Liang Tao^1,2,3,*

¹Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
²Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
³Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
⁴Department of Urology, Boston Children’s Hospital, Boston, MA, USA
⁵Department of Surgery and Department of Microbiology, Harvard Medical School, Boston, MA, USA
These authors contributed equally: Yao Zhou, Diyin Li, Jianhua Luo Correspondence: Liang Tao(taoliang@westlake.edu.cn)

Dear Editor,

Clostridium novyi (C. novyi) is a spore-forming anaerobic bacterium and opportunistic pathogen causing severe infectious diseases in humans and animals including gas gangrene, myositis, necrotic hepatitis, and sepsis.1,2 The alpha-toxin (Tcnα) is the major virulence factor of C. novyi and is produced by all known pathogenic C. novyi types.1 Tcnα belongs to the large clostridial toxin (LCT) family which also includes Clostridioides difficile toxin A (TcdA) and toxin B (TcdB), Paeniclostridium sordellii lethal toxin (TcsL) and hemorrhagic toxin (TcsH), and Clostridium perfringens large cytotoxin (TpeL). Like other LCTs, Tcnα binds to the surface of the target cell and enters the cell via receptor-mediated endocytosis. The enzymatic domain is then delivered into the cytosol and glucosylates small Rho-family GTPases using UDP-N-acetylglucosamine as a co-substrate, leading to cytoskeleton disruption and cell death.3 Recently, the cellular receptors of several LCTs, including TpeL, TcdB, TcdA, and TcsL have been identified.4,5,6,7,8,9,10 Tcnα and TcsH are the only two major members of the LCT family with their host receptors remaining unclear.

https://doi.org/10.1038/s41422-021-00510-z

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