Alouf J
Institut Pasteur de Lille.
C R Seances Soc Biol Fil. 1998;192(3):485-502.
Among the 315 protein toxins elicited by gram positive and gram negative bacteria so far characterized, about 50 toxins are currently considered as totally or partially, responsible of the pathological manifestations and/or lethality resulting from host infection or intoxication (contaminated food) by relevant toxinogenic bacteria. A certain number of criteria are required for the assessment of indisputable involvement of a toxin or an array of toxins (from the same bacteria) in infectious diseases: 1) The bacterial microorganism clearly identified as the pathogenic agent of the disease produces component(s) considered as toxin(s); 2) The administration to appropriate animal(s) of the toxin(s) separated from the relevant bacteria or produced by genetic engineering from a heterologous tox+ recombinant bacterial strain produces symptoms and pathophysiological disorders that mimic those observed in the natural disease or at least those elicited in experimental animals by the cognate toxin-producing bacteria; 3) The in vitro incubation of the isolated toxin(s) with appropriate animal organs, tissues or cells elicits certain pathophysiological, biochemical or metabolic manifestions observed in the host infected with the relevant toxinogenic bacteria; 4) Toxin concentration in the organism of the host infected by the toxinogenic bacteria should be compatible with the characteristics of the relevant disease. The toxins of pathogenic interest exhibit a variety of effects in bacterial diseases. Bacteria that colonize a wound or mucosal surface but do not invade target cells can produce toxins that act locally or enter the bloodstream and attack internal organs (e.g. Corynebacterium diphtheriae, Vibrio cholerae, ...). Bacteria growing in a wound can produce toxins that destroy host tissue and kill phagocytes in the immediate vicinity of the bacteria, thus facilitating bacterial growth and spread. On the basis of the above mentioned criteria, the following bacterial diseases among many others are toxin-associated (toxinoses): diphtheria, tetanus, botulism, whooping cough, diarrhea, bloody diarrhea, hemolytic uremic syndrome, cholera, scarlet fever, toxic shock syndrome, gas gangrene, B. fragilis diarrhea, anthrax, pseudomembranous colitis.
在目前已鉴定的由革兰氏阳性菌和革兰氏阴性菌产生的315种蛋白质毒素中,约有50种毒素目前被认为全部或部分地导致了宿主感染或因相关产毒素细菌中毒(食用受污染食物)所引发的病理表现和/或致死性。评估一种毒素或一系列毒素(来自同一细菌)在传染病中无可争议的作用需要一定数量的标准:1)被明确鉴定为该疾病病原体的细菌微生物产生被视为毒素的成分;2)将从相关细菌中分离出的毒素或通过基因工程从异源产毒素重组细菌菌株产生的毒素给予适当的动物,会产生与自然疾病中观察到的症状和病理生理紊乱相似的症状,或者至少与同源产毒素细菌在实验动物中引发的症状相似;3)将分离出的毒素与适当的动物器官、组织或细胞进行体外孵育,会引发在感染相关产毒素细菌的宿主中观察到的某些病理生理、生化或代谢表现;4)被产毒素细菌感染的宿主生物体中的毒素浓度应与相关疾病的特征相符。具有致病意义的毒素在细菌性疾病中表现出多种作用。定殖于伤口或粘膜表面但不侵入靶细胞的细菌可产生作用于局部或进入血液并攻击内部器官的毒素(如白喉棒状杆菌、霍乱弧菌等)。在伤口中生长的细菌可产生破坏宿主组织并杀死细菌附近吞噬细胞的毒素,从而促进细菌的生长和扩散。基于上述标准,许多其他细菌性疾病中,以下这些是与毒素相关的(毒素病):白喉、破伤风、肉毒中毒、百日咳、腹泻、血性腹泻、溶血性尿毒症综合征、霍乱、猩红热、中毒性休克综合征、气性坏疽、脆弱拟杆菌腹泻、炭疽、假膜性结肠炎。