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霍乱弧菌O139孟加拉型的流行病学与分子生物学

Epidemiology & molecular biology of Vibrio cholerae O139 Bengal.

作者信息

Albert M J

机构信息

Laboratory Sciences Division, International Centre for Diarrhoeal Disease Research Bangladesh (ICDDR,B), Dhaka, Bangladesh.

出版信息

Indian J Med Res. 1996 Jul;104:14-27.

PMID:8783504
Abstract

The emergence of Vibrio cholerae O139 Bengal as the second aetiologic agent of epidemic cholera in October 1992 in the south Indian coastal city of Madras has shattered the long-held notion that only V. cholerae belonging to serogroup O1 are capable of causing epidemic (and pandemic) cholera. Within months of its appearance in Madras, V. cholerae O139 engulfed the entire Indian subcontinent in a series of outbreaks of cholera. It also spread to several neighbouring countries in Asia. Several western countries also reported imported cholera cases due to this organism. In the regions of the Indian subcontinent where cholera due to V. cholerae O1 is endemic, children are mostly susceptible because adults would have acquired at least some immunity due to earlier exposure. However, when V. cholerae O139 struck people in these areas, even though all age groups were affected, the disease was more prevalent in adults, which suggested that the disease is new in this population. As with O1 cholera, water and food seemed to be the vehicles of infection. Many family contracts of index cases of O139 cholera were found to be infected with V. cholerae O139, and in many of them, the infection was asymptomatic which is reminiscent of O1 EITor infection. Again as with O1 EITor infection, individuals of blood group O were more susceptible to O139 infection than those with other blood groups. In its molecular aspects, O139 vibrio resembles O1 EITor vibrio. The virulence genes encoding cholera toxin, zonula occludens toxin, accessory cholera enterotoxin and core-encoded pilin are present in a 4.5 kb 'virulence cassette' region of the chromosome as in EITor vibrios and the expression of these virulence factors, toxin coregulated pilus (TCP) and several outer membrane proteins are found to be under the control of the master regulator ToxR as in EITor vibrios. The iron-regulated genes involved in virulence are also found in the same locus as in EITor vibrios. However, the genes involved in the somatic antigen synthesis in O1 vibrios are found to be deleted in O139 vibrios and are replaced by a new region of chromosome which encodes the new surface antigen synthesis in O139 vibrios. When V. cholerae O139 emerged and caused outbreaks, the prevailing O1 EITor vibrios virtually disappeared from most of the areas. The disappearance of EITor vibrios, the rapid spread of O139 vibrios and the resemblance of O139 vibrios to EITor vibrios seemed to suggest that O139 vibrios might be the causative agent of the 'eighth' pandemic of cholera. However, after a year of its appearance, O139 vibrios are on the wane and O1 EITor vibrios have re-emerged as the predominant organism, in the Indian subcontinent. Thus, the immediate threat of a new cholera pandemic posed by V. cholerae O139 may not be as large as it first seemed. However, whether it will follow the pattern of EITor vibrio which took approximately 60 yr since its first isolation before emerging as the seventh pandemic strain of cholera, is not clear. The factor(s) contributing to the diminished isolation of O139 vibrios and the re-emergence of O1 EITor vibrios are not understood. The vibrios might have undergone changes that would have affected their ability to survive and compete in the environment.

摘要

1992年10月,霍乱弧菌O139孟加拉型在印度南部沿海城市马德拉斯作为霍乱流行的第二种病原体出现,这打破了长期以来的观念,即只有O1血清群的霍乱弧菌能够引起霍乱流行(和大流行)。在马德拉斯出现后的几个月内,O139霍乱弧菌在一系列霍乱疫情中席卷了整个印度次大陆。它还传播到亚洲的几个邻国。几个西方国家也报告了由这种病原体引起的输入性霍乱病例。在印度次大陆O1霍乱弧菌地方性流行的地区,儿童大多易感,因为成年人由于早期接触至少会获得一些免疫力。然而,当O139霍乱弧菌侵袭这些地区的人群时,尽管所有年龄组都受到影响,但该疾病在成年人中更为普遍,这表明这种疾病在这一人群中是新出现的。与O1霍乱一样,水和食物似乎是感染的传播媒介。许多O139霍乱首例病例的家庭接触者被发现感染了O139霍乱弧菌,其中许多人感染后无症状,这让人联想到O1埃尔托型感染。同样与O1埃尔托型感染一样,O血型的个体比其他血型的个体更容易感染O139。在分子层面,O139弧菌与O1埃尔托弧菌相似。编码霍乱毒素、小带闭合毒素、辅助霍乱肠毒素和核心编码菌毛的毒力基因存在于染色体的一个4.5 kb“毒力盒”区域,就像在埃尔托弧菌中一样,并且发现这些毒力因子、毒素共调节菌毛(TCP)和几种外膜蛋白的表达受主调节因子ToxR的控制,就像在埃尔托弧菌中一样。与毒力有关的铁调节基因也在与埃尔托弧菌相同的位点被发现。然而,发现O1弧菌中参与菌体抗原合成的基因在O139弧菌中缺失,并被一个新的染色体区域取代,该区域编码O139弧菌中的新表面抗原合成。当O139霍乱弧菌出现并引发疫情时,当时流行的O1埃尔托弧菌实际上在大多数地区消失了。埃尔托弧菌的消失、O139弧菌的迅速传播以及O139弧菌与埃尔托弧菌的相似性似乎表明O139弧菌可能是霍乱“第八次”大流行的病原体。然而,在其出现一年后,O139弧菌逐渐减少,而O1埃尔托弧菌在印度次大陆再次成为主要菌株。因此,O139霍乱弧菌引发新的霍乱大流行的直接威胁可能没有最初看起来那么大。然而,它是否会遵循埃尔托弧菌的模式,即从首次分离到成为霍乱第七次大流行菌株大约经历了60年,尚不清楚。导致O139弧菌分离减少和O1埃尔托弧菌再次出现的因素尚不清楚。这些弧菌可能发生了变化,影响了它们在环境中的生存和竞争能力。

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