Tetanus vaccination is of major importance for public health in most countries in the world. The World Health Organization indicated that 15,000 tetanus cases were reported in 2018 (World Health Organization, 2019). Currently, vaccine manufacturers use tetanus toxin produced by Clostridium tetani fermentation in complex media. The complex components, commonly derived from animal sources, introduce potential variability in cultures. To achieve replicable fermentation and to avoid toxic or allergic reactions from animal-source compounds, several studies have tried to switch from complex to chemically defined media without affecting toxin titers. The present review introduces the current knowledge on i) C. tetani strain diversity, whole-genome sequences and metabolic networks; ii) toxin regulation and synthesis; and iii) culture media, cultivation processes and growth requirements. We critically reviewed the reported data on metabolism in C. tetani and completed comparative genomic and proteomic analyses with other Clostridia species. We integrated genomic data based on whole-genome sequence annotation, supplemented with cofactor specificities determined by protein sequence identity, in a new map of C. tetani central metabolism. This is the first data review that integrates insights from omics experiments on C. tetani. The overview of C. tetani physiology described here could provide support for the design of new chemically defined media devoid of complex sources for toxin production.

破伤风疫苗接种对世界上大多数国家的公共卫生具有重要意义。世界卫生组织表示，2018 年报告了 15,000 例破伤风病例（世界卫生组织，2019）。目前，疫苗制造商使用破伤风梭菌在复杂培养基中发酵产生的破伤风毒素。复杂的成分，通常来源于动物，在文化中引入了潜在的变异性。为了实现可复制的发酵并避免来自动物源化合物的毒性或过敏反应，一些研究试图在不影响毒素滴度的情况下从复杂培养基切换到化学成分确定的培养基。本综述介绍了目前关于 i)破伤风杆菌的知识菌株多样性、全基因组序列和代谢网络；ii) 毒素调节和合成；iii) 培养基、培养过程和生长要求。我们严格审查了已报道的破伤风梭菌代谢数据，并完成了与其他梭菌属物种的比较基因组和蛋白质组学分析。我们在新的破伤风梭菌中心代谢图谱中整合了基于全基因组序列注释的基因组数据，并辅以由蛋白质序列同一性确定的辅因子特异性。这是第一次整合来自破伤风梭菌组学实验的见解的数据审查。破伤风杆菌概述这里描述的生理学可以为设计新的化学成分确定的培养基提供支持，该培养基没有复杂的毒素产生来源。