Smedley J G, Fisher D J, Sayeed S, Chakrabarti G, McClane B A
University of Pittsburgh School of Medicine, Department of Molecular Genetics and Biochemistry, Pittsburgh, PA 15261, USA.
Rev Physiol Biochem Pharmacol. 2004;152:183-204. doi: 10.1007/s10254-004-0036-2. Epub 2004 Oct 23.
The Gram-positive pathogen Clostridium perfringens is a major cause of human and veterinary enteric disease largely because this bacterium can produce several toxins when present inside the gastrointestinal tract. The enteric toxins of C. perfringens share two common features: (1) they are all single polypeptides of modest (approximately 25-35 kDa) size, although lacking in sequence homology, and (2) they generally act by forming pores or channels in plasma membranes of host cells. These enteric toxins include C. perfringens enterotoxin (CPE), which is responsible for the symptoms of a common human food poisoning and acts by forming pores after interacting with intestinal tight junction proteins. Two other C. perfringens enteric toxins, epsilon-toxin (a bioterrorism select agent) and beta-toxin, cause veterinary enterotoxemias when absorbed from the intestines; beta- and epsilon-toxins then apparently act by forming oligomeric pores in intestinal or extra-intestinal target tissues. The action of a newly discovered C. perfringens enteric toxin, beta2 toxin, has not yet been defined but precedent suggests it might also be a pore-former. Experience with other clostridial toxins certainly warrants continued research on these C. perfringens enteric toxins to develop their potential as therapeutic agents and tools for cellular biology.
革兰氏阳性病原菌产气荚膜梭菌是人和兽医肠道疾病的主要病因,很大程度上是因为这种细菌在胃肠道内时可产生多种毒素。产气荚膜梭菌的肠道毒素有两个共同特征:(1)它们都是大小适中(约25 - 35 kDa)的单一多肽,尽管缺乏序列同源性;(2)它们通常通过在宿主细胞质膜上形成孔道来发挥作用。这些肠道毒素包括产气荚膜梭菌肠毒素(CPE),它是人类常见食物中毒症状的罪魁祸首,通过与肠道紧密连接蛋白相互作用后形成孔道来发挥作用。另外两种产气荚膜梭菌肠道毒素,ε毒素(一种生物恐怖主义筛选剂)和β毒素,从肠道吸收后会导致兽医肠毒血症;β毒素和ε毒素显然通过在肠道或肠道外靶组织中形成寡聚孔道来发挥作用。新发现的产气荚膜梭菌肠道毒素β2毒素的作用尚未明确,但先例表明它可能也是一种孔形成毒素。对其他梭菌毒素的研究经验确实值得继续对这些产气荚膜梭菌肠道毒素进行研究,以开发它们作为治疗剂和细胞生物学工具的潜力。