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揭开毒力的隐藏凭证。

Uncovering the Hidden Credentials of Virulence.

机构信息

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.

出版信息

Microbiol Mol Biol Rev. 2021 Feb 10;85(1). doi: 10.1128/MMBR.00021-19. Print 2021 Feb 17.

Abstract

Bacteria in the genus are important human and veterinary pathogens. The abortion and infertility they cause in food animals produce economic hardships in areas where the disease has not been controlled, and human brucellosis is one of the world's most common zoonoses. strains have also been isolated from wildlife, but we know much less about the pathobiology and epidemiology of these infections than we do about brucellosis in domestic animals. The brucellae maintain predominantly an intracellular lifestyle in their mammalian hosts, and their ability to subvert the host immune response and survive and replicate in macrophages and placental trophoblasts underlies their success as pathogens. We are just beginning to understand how these bacteria evolved from a progenitor alphaproteobacterium with an environmental niche and diverged to become highly host-adapted and host-specific pathogens. Two important virulence determinants played critical roles in this evolution: (i) a type IV secretion system that secretes effector molecules into the host cell cytoplasm that direct the intracellular trafficking of the brucellae and modulate host immune responses and (ii) a lipopolysaccharide moiety which poorly stimulates host inflammatory responses. This review highlights what we presently know about how these and other virulence determinants contribute to pathogenesis. Gaining a better understanding of how the brucellae produce disease will provide us with information that can be used to design better strategies for preventing brucellosis in animals and for preventing and treating this disease in humans.

摘要

属中的细菌是重要的人类和兽医病原体。它们在食用动物中引起的流产和不育会给疾病尚未得到控制的地区带来经济困难,而人类布鲁氏菌病是世界上最常见的人畜共患病之一。野生动物也分离到了 菌株,但我们对这些感染的病理生物学和流行病学的了解远不及对家畜布鲁氏菌病的了解。布鲁氏菌在其哺乳动物宿主中主要维持一种细胞内生活方式,它们能够颠覆宿主的免疫反应,并在巨噬细胞和胎盘滋养层中存活和复制,这是它们作为病原体成功的基础。我们才刚刚开始了解这些细菌是如何从具有环境生态位的祖先α变形菌进化而来,并分化为高度适应宿主和宿主特异性的病原体的。两个重要的毒力决定因素在这一进化过程中起着关键作用:(i)一种 IV 型分泌系统,它将效应分子分泌到宿主细胞质中,指导布鲁氏菌的细胞内运输,并调节宿主的免疫反应;(ii)一个脂多糖部分,它不能很好地刺激宿主的炎症反应。这篇综述强调了我们目前对这些和其他毒力决定因素如何导致发病机制的了解。更好地了解布鲁氏菌如何引起疾病,将为我们提供信息,用于设计更好的策略来预防动物中的布鲁氏菌病,以及预防和治疗人类中的这种疾病。

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