"Black holes" and bacterial pathogenicity:: A large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli
"Black holes" and bacterial pathogenicity:: A large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli
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DOI：
10.1073/pnas.95.7.3943
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发表时间：
1998-03-31
影响因子：
11.1
通讯作者：
Fasano, A
中科院分区：
文献类型：
--
作者：
Maurelli, AT;Fernández, RE;Fasano, A
质粒、噬菌体和致病性岛是有助于细菌病原体进化的基因组添加物，例如志贺氏菌属，作为细菌性痢疾的病原体，与密切相关的大肠杆菌不同之处在于志贺氏菌中存在编码毒力功能的质粒。然而，致病菌也可能缺乏非病原体的特性。赖氨酸脱羧酶（LDC）活性存在于约90%的E.将LDC基因cadA导入福氏2a志贺菌后，毒力减弱，肠毒素活性受到明显抑制，其肠毒素抑制剂经鉴定为LDC催化反应的产物尸胺。flexneri 2a和实验室E. coliK-12基因组cadA区域在志贺菌中发现了一个大的缺失。和肠侵袭性E. coli中cadA基因也有类似的缺失。由E.大肠杆菌成为病原体时，它们不仅在质粒上获得了毒力基因，而且还通过缺失来释放基因。这些“黑洞”的形成，即对病原体生活方式有害的基因的缺失，提供了一条使病原体能够增强毒力的进化途径，此外，尸胺可以抑制肠毒素活性的证明可能导致关于毒素活性或进入细胞的更一般的模型，因此，了解黑洞在病原体进化中的作用可能会为传染病的新治疗提供线索。
Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens, For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions, However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in approximate to 90% of E. coli strains but is uniformly absent in Shigella strains, When the gene for LDC, cadA, was introduced into Shigella flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited greatly, The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC, Comparison of the S. flexneri 2a and laboratory E. coli K-12 genomes in the region of cadA revealed a large deletion in Shigella, Representative strains of Shigella spp. and enteroinvasive E. coli displayed similar deletions of cadA, Our results suggest that, as Shigella spp. evolved from E. coli to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions, The formation of these "black holes," deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence, Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy, Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases.