It is estimated that approximately one billion people are at risk of infection with obligate intracellular bacteria, but little is known about the underlying mechanisms that govern their life cycles. The difficulty in studying Chlamydia spp., Coxiella spp., Rickettsia spp., Anaplasma spp., Ehrlichia spp. and Orientia spp. is, in part, due to their genetic intractability. Recently, genetic tools have been developed; however, optimizing the genomic manipulation of obligate intracellular bacteria remains challenging. In this Review, we describe the progress in, as well as the constraints that hinder, the systematic development of a genetic toolbox for obligate intracellular bacteria. We highlight how the use of genetically manipulated pathogens has facilitated a better understanding of microbial pathogenesis and immunity, and how the engineering of obligate intracellular bacteria could enable the discovery of novel signalling circuits in host–pathogen interactions.

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专心的细胞内细菌工程：进展，挑战和范例

据估计，约有十亿人处于感染专性细胞内细菌的危险中，但是对于控制其生命周期的潜在机制知之甚少。研究衣原体，科氏杆菌属的困难。，立克次体，无形体，埃里希氏菌。和东方spp。部分是由于它们的遗传难处理性。最近，已经开发了遗传工具。然而，优化专性细胞内细菌的基因组操作仍然具有挑战性。在这篇综述中，我们描述了专性细胞内细菌的遗传工具箱的系统发展以及阻碍其发展的因素。我们着重介绍了使用遗传操纵的病原体如何促进对微生物发病机理和免疫力的更好理解，以及专性细胞内细菌的工程改造如何能够发现宿主与病原体相互作用中的新型信号传导回路。