Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses and are among the oldest known vector-borne pathogens. Members of this genus are extraordinarily diverse and exhibit a broad host range. To establish intracellular infection, Rickettsia species undergo complex, multistep life cycles that are encoded by heavily streamlined genomes. As a result of reductive genome evolution, rickettsiae are exquisitely tailored to their host cell environment but cannot survive extracellularly. This host-cell dependence makes for a compelling system to uncover novel host–pathogen biology, but it has also hindered experimental progress. Consequently, the molecular details of rickettsial biology and pathogenesis remain poorly understood. With recent advances in molecular biology and genetics, the field is poised to start unraveling the molecular mechanisms of these host–pathogen interactions. Here, we review recent discoveries that have shed light on key aspects of rickettsial biology. These studies have revealed that rickettsiae subvert host cells using mechanisms that are distinct from other better-studied pathogens, underscoring the great potential of the Rickettsia genus for revealing novel biology. We also highlight several open questions as promising areas for future study and discuss the path toward solving the fundamental mysteries of this neglected and emerging human pathogen.

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立克次体的神秘生物学：最新进展、开放性问题和展望

立克次体是专性细胞内细菌，可导致危及生命的疾病，是已知最古老的病媒传播病原体之一。该属的成员非常多样化，并且表现出广泛的寄主范围。为了建立细胞内感染，立克次体物种经历了由高度精简的基因组编码的复杂、多步骤的生命周期。作为还原基因组进化的结果，立克次氏体经过精心调整以适应其宿主细胞环境，但不能在细胞外存活。这种宿主-细胞依赖性为揭示新的宿主-病原体生物学提供了一个引人注目的系统，但它也阻碍了实验的进展。因此，立克次体生物学和发病机制的分子细节仍然知之甚少。随着分子生物学和遗传学的最新进展，该领域准备开始解开这些宿主-病原体相互作用的分子机制。在这里，我们回顾了阐明立克次体生物学关键方面的最新发现。这些研究表明，立克次体使用不同于其他研究得更充分的病原体的机制破坏宿主细胞，强调了立克次体属在揭示新生物学方面的巨大潜力。我们还强调了几个悬而未决的问题作为未来研究的有希望的领域，并讨论了解决这种被忽视和新兴的人类病原体的基本谜团的途径。这些研究表明，立克次体使用不同于其他研究得更充分的病原体的机制破坏宿主细胞，强调了立克次体属在揭示新生物学方面的巨大潜力。我们还强调了几个悬而未决的问题作为未来研究的有希望的领域，并讨论了解决这种被忽视和新兴的人类病原体的基本谜团的途径。这些研究表明，立克次体使用不同于其他研究得更充分的病原体的机制破坏宿主细胞，强调了立克次体属在揭示新生物学方面的巨大潜力。我们还强调了几个悬而未决的问题作为未来研究的有希望的领域，并讨论了解决这种被忽视和新兴的人类病原体的基本谜团的途径。