Bacteria in the genus Brucella 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. Brucella 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 Brucella 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.

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揭开布鲁氏菌毒力的隐藏凭证

布鲁氏菌属细菌是重要的人类和兽医病原体。它们在食用动物中造成的流产和不育在疾病尚未得到控制的地区造成经济困难，而人类布鲁氏菌病是世界上最常见的人畜共患病之一。布鲁氏菌菌株也已从野生动物中分离出来，但我们对这些感染的病理生物学和流行病学的了解远远少于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细胞内生活方式，它们破坏宿主免疫反应并在巨噬细胞和胎盘滋养层中生存和复制的能力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 alphaproteobacterium 进化而来的，然后分化为高度适应宿主和宿主特异性的病原体。两个重要的毒力决定因素在这一演变中发挥了关键作用：(i) 一种 IV 型分泌系统，可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免疫反应，以及 (ii) 一种对宿主炎症反应刺激作用较差的脂多糖部分。这篇综述重点介绍了我们目前对这些和其他毒力决定因素如何促成布鲁氏菌发病机制。更好地了解布鲁氏菌如何产生疾病将为我们提供信息，这些信息可用于设计预防动物布鲁氏菌病以及预防和治疗人类布鲁氏菌病的更好策略。