EXPERIMENTAL MODELS IN INVESTIGATION OF VIRULENCE OF DYSENTERY BACILLI AND ESCHERICHIA-COLI
EXPERIMENTAL MODELS IN INVESTIGATION OF VIRULENCE OF DYSENTERY BACILLI AND ESCHERICHIA-COLI
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DOI：
10.1111/j.1749-6632.1971.tb35004.x
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发表时间：
1971-01-01
影响因子：
5.2
通讯作者：
LABREC, EH
中科院分区：
文献类型：
--
作者：
FORMAL, SB;DUPONT, HL;LABREC, EH
从实验室模型实验中获得的知识对我们目前对一些人类腹泻疾病的发病机制的理解非常有用。细菌性痢疾尤其如此。痢疾可定义为水样便中含有血液、炎症细胞和粘液的一种综合征。典型志贺氏菌病的一个主要特征是结肠粘膜溃疡性病变，因为红细胞正是通过上皮屏障的这种缺陷到达肠腔的。因此，为了深入了解经典细菌性痢疾发病机制的至少一个方面，必须了解溃疡性病变是如何演变的。先前关于结肠溃疡演变的概念设想了热稳定性毒素在肠壁上的连续吸收和排泄，导致上皮缺氧和死亡。由于种种原因，我们拒绝了这一假设，并寻求另一种解释。我们首先使用了一种强毒的福氏志贺氏菌2a菌株和由它衍生的一种无毒突变株。就目前所能确定的情况而言，这两种菌株是相同的，唯一的例外是，当把亲本菌株喂给饥饿的、服用鸦片的豚鼠或恒河猴时，会引起疾病，而突变株则没有这样做。当使用荧光抗体技术研究感染任一菌株的动物时，观察到生物体在肠道中的分布模式明显不同。无毒突变株仅在肠腔中可见。另一方面，毒杆菌存在于肠上皮细胞中，也存在于固有层的游离细胞和吞噬细胞中。很少在粘膜下层或肠系膜淋巴结中观察到微生物。从这些实验结果我们得出结论，细菌性痢疾发病的一个重要步骤是病原体对肠上皮细胞的渗透。如果生物体由于这样或那样的原因不能进入上皮，很少观察到疾病的迹象。Voino-Yasenetsky和Khavkin独立地进行了类似的观察，并在Ogawa及其同事的广泛研究中得到证实。^有其他方法可测试痢疾杆菌的能力
The knowledge gained from experiments in laboratory models has been very useful in helping us to reach our present understanding of the pathogenesis of some diarrheal diseases of human beings. This is especially true of bacillary dysentery. Dysentery may be defined as a syndrome in which blood, inflammatory cells, and mucus are present in the watery stool. A cardinal feature of classical shigellosis is an ulcerative lesion of the colonic mucosa, for it is through this defect in the epithelial barrier that the red blood cells reach the intestinal lumen. Thus, in order to gain some insight into at least one aspect of the pathogenesis of classical bacillary dysentery, one must understand how the ulcerative lesion evolves.The previous concept of the evolution of the colonic ulcer envisioned consecutive waves of absorption and excretion of heat-stable toxin across the intestinal wall, resulting in hypoxia and death of the epithe1ium. l For a variety of reasons2 we rejected this hypothesis and sought an alternate explanation. We started by using a virulent Shigella flexneri 2a strain and an avirulent mutant derived from it. As far as could be ascertained, the two strains were identical, with the exception that the parent strain caused disease when fed to starved, opiated guinea pigs or to rhesus monkeys, while the mutant failed to do so. When animals infected with either of the strains were studied using the fluorescent antibody technique, a distinctly different pattern of distribution of the organisms in the intestine was observed. The avirulent mutant was seen only in the lumen of the bowel. On the other hand the virulent bacteria were present in the epithelial cells of the intestine, and also both free and within phagocytic cells in the lamina propria. Rarely were the organisms viewed in the submucosa or in the mesenteric lymph nodes. 2 From the results of these experiments we concluded that an essential step in the pathogenesis of bacillary dysentery is the penetration of the intestinal epithelial cell by the pathogen. If the organism is unable to enter the epithelium for one reason or another, few, if any, signs of disease are observed. Similar observations have been made independently by Voino-Yasenetsky and Khavkin and confirmed in extensive studies by Ogawa and colleague^.^ Other procedures are available to test for the ability of dysentery bacilli to