肉毒神经毒素:一个老毒素的新密码

Botulinum neurotoxins:the new for the old

肉毒梭菌长期进化形成了独特的旱地(草地)和湿地两套自然循环机制,厌氧和产芽胞是成就其自然循环最合理的进化选择.肉毒梭菌本身无侵袭力,致病性全取决于毒素,即肉毒神经毒素(肉毒素)(botulinum neurotoxins,BoNTs,botulin),致野生及家养脊椎动物肉毒中毒(botulism).据肉毒素抗原性将其分为不同的血清型(毒素型),目前已鉴定的毒素血清型已超过40个,产生肉毒素的细菌按遗传关系可分为7个种.毒素抗原性虽不同,但空间结构均相似,均含3个功能域:HC受体结合域、HN穿膜域和LC活性域.BoNTs-LC具Zn^(2+)依赖蛋白酶活性,降解外周运动神经元的突触融合复合体蛋白,从而阻断神经递质释放,致肌肉麻痹.

Clostridium botulinum has evolved perfect natural cycle for both dry land/grassland and wet land/aquatic ecosystem through a long history,which are achieved by the most appropriate evolutionary choices,the two life features,sporulation and anaerobic respiration.C.botulinumis pathogenic,causing botulism mostly affects wild and domesticated animals,completely owing to the release of botulinum neurotoxins(BoNTs)rather than invasiveness.There are more than 40 different BoNT types based on antigenicity differences produced by 7phylogenetically distinct species.Although with different antigenicities,all BoNTs shared common structural features,including three domains:HC/binding,HN/transmemberane and LC/active domain.The metalloprotease activity of BoNTs-LC specifically cleaves the SNARE(soluble N-ethylmaleimide-sensitive factor attachment protein receptor)proteins that are necessary for neurotransmitter exocytosis which inactivate neurotransmitter release leading to persistent paralysis of peripheral nerve terminals and connected muscles.