van Schaik Erin J, Case Elizabeth D, Martinez Eric, Bonazzi Matteo, Samuel James E
Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Bryan, TX, USA.
Centre National de la Recherche Scientifique, Formation de Recherche en Évolution 3689, Centre d'études d'agents Pathogènes et Biotechnologies Pour la Santé, Université Montpellier Montpellier, France.
Front Cell Infect Microbiol. 2017 Feb 3;7:25. doi: 10.3389/fcimb.2017.00025. eCollection 2017.
is an intracellular, zoonotic pathogen that is the causative agent of Q fever. Infection most frequently occurs after inhalation of contaminated aerosols, which can lead to acute, self-limiting febrile illness or more serve chronic infections such as hepatitis or endocarditis. Macrophages are the principal target cells during infection where resides and replicates within a unique phagolysosome-like compartment, the -containing vacuole (CCV). The first virulence determinant described as necessary for infection was full-length lipopolysaccarride (LPS); spontaneous rough mutants (phase II) arise after passage in immuno-incompetent hosts. Phase II are attenuated in immuno-competent animals, but are fully capable of infecting a variety of host cells . A clonal strain of the Nine Mile isolate (RSA439, clone 4), has a 26 KDa chromosomal deletion that includes LPS biosynthetic genes and is uniquely approved for use in BL2/ABL2 conditions. With the advances of axenic media and genetic tools for research, the characterization of novel virulence determinants is ongoing and almost exclusively performed using this attenuated clone. A major problem with predicting essential virulence loci with RSA439 is that, although some cell-autonomous phenotypes can be assessed in tissue culture, no animal model for assessing pathogenesis has been defined. Here we describe the use of SCID mice for predicting virulence factors of , in either independent or competitive infections. We propose that this model allows for the identification of mutations that are competent for intracellular replication , but attenuated for growth and predict essential innate immune responses modulated by the pathogen during infection as a central pathogenic strategy.
是一种细胞内人畜共患病原体，是Q热的病原体。感染最常发生在吸入受污染的气溶胶后，这可能导致急性自限性发热疾病或更严重的慢性感染，如肝炎或心内膜炎。巨噬细胞是感染期间的主要靶细胞，病原体在其中一个独特的类似吞噬溶酶体的区室即含病原体液泡（CCV）中驻留并复制。被描述为感染所必需的第一个毒力决定因素是全长脂多糖（LPS）；在免疫缺陷宿主中传代后会出现自发粗糙突变体（II期）。II期在免疫健全的动物中减毒，但完全能够感染多种宿主细胞。九英里分离株（RSA439，克隆4）的一个克隆菌株有一个26 kDa的染色体缺失，包括LPS生物合成基因，并且唯一被批准用于BL2/ABL2条件。随着用于病原体研究的无菌培养基和遗传工具的进步，新型毒力决定因素的表征正在进行，并且几乎完全使用这种减毒克隆进行。用RSA439预测必需毒力位点的一个主要问题是，尽管一些细胞自主表型可以在组织培养中评估，但尚未定义用于评估发病机制的动物模型。在这里，我们描述了使用SCID小鼠在独立或竞争性感染中预测病原体的毒力因子。我们提出，这个模型允许识别能够在细胞内复制但在生长方面减毒的突变，并预测病原体在感染期间调节的基本先天免疫反应是一种核心致病策略。
