TcdB From Hypervirulent <i>Clostridioides difficile</i> Induces Neuronal Loss and Neurotransmitter Alterations in the Intrinsic Enteric Nervous System
Clostridioides difficile infection (CDI) is a predominant cause of intestinal infections. The intrinsic enteric nervous system (ENS) occupies the intestinal tissue in large numbers and intricately regulates various aspects of intestinal function. Nonetheless, the specific effects of CDI on the intrinsic ENS remain underexplored. Herein, we employed the toxin B variant (TcdB2) derived from hypervirulent C difficile to elucidate the impact of CDI on neurons located in colonic wall. We found that TcdB2 directly induced dose-dependent cytopathic effects on enteric neurons both in vitro and in adult mice colons. Notably, an increased expression of choline acetyltransferase and neural nitric oxide synthase in colonic neurons prior to the onset of cytopathic changes following treatment with TcdB2 were observed, both in vivo and in vitro. These findings suggest that during CDI, TcdB not only causes neuronal loss but also alters the composition of neurotransmitters in the ENS.
Authors
- Wei Chen (ORCID: https://orcid.org/0000-0001-7438-3241)
- Shuangshuang Wan (ORCID: https://orcid.org/0009-0005-7619-3325)
- Dazhi Jin (ORCID: https://orcid.org/0000-0002-2613-7844)
- L.W. Chen
- Zhai Hong (ORCID: https://orcid.org/0000-0001-9993-8557)
- Kai Zhang (ORCID: https://orcid.org/0000-0001-8581-9063)
- Yu Chen (ORCID: https://orcid.org/0000-0001-8484-040X)
- Ming Yang (ORCID: https://orcid.org/0000-0002-2954-7435)
- Qi Zhou (ORCID: https://orcid.org/0000-0001-5653-160X)
- Feng Zhang (ORCID: https://orcid.org/0000-0002-1978-3821)
- Yongneng Luo
- Gu Hanyang
- Hui Hu (ORCID: https://orcid.org/0000-0002-3440-5415)
- Xinghao Lin
- Mengjie Wang (ORCID: https://orcid.org/0000-0003-2124-3215)
Institutions
- Shaoxing University (CN)
- Shanghai Public Health Clinical Center (CN)
- Blood Center of Zhejiang Province (CN)
- Zhejiang Academy of Medical Sciences (CN)
- Zhejiang Provincial People's Hospital (CN)
- Shanghai University of Medicine and Health Sciences (CN)
- Center for Life Sciences (CN)
- Hangzhou Medical College (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- The Journal of Infectious Diseases
- Published
- 2024-10-14
- DOI
- https://doi.org/10.1093/infdis/jiae498
- Citations
- 3
- Primary Topic
- Clostridium difficile and Clostridium perfringens research
- Type
- article
- Field-Weighted Citation Impact
- 1.17