Metabolic Plasticity Aids Amphotropism of Coxiella burnetii.
Metabolic Plasticity Aids Amphotropism of Coxiella burnetii.
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DOI：
10.1128/iai.00135-21
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发表时间：
2021-11-16
影响因子：
3.1
通讯作者：
Omsland A
中科院分区：
文献类型：
--
作者：
Sanchez SE;Goodman AG;Omsland A
贝氏柯克斯体（Coxiella burnetii）是一种专性胞内细菌，是引起人类Q热的病原体。C.贝氏体可以天然感染广泛的宿主生物（例如，哺乳动物和节肢动物）和细胞类型。C. Burnetii结合其利用糖酵解和产气碳源的能力，表明病原体依赖于代谢可塑性在营养多样的细胞内环境中复制。探讨代谢可塑性在C. burnetii宿主细胞定殖、C.在7个不同的细胞系中，比较了贝氏体在具有代谢能力的亲本菌株和不能进行异源发生的突变体CbΔpckA之间的细胞内复制。亲本菌株和CbΔpckA突变体均表现出宿主细胞依赖性感染表型，其受宿主糖酵解或产酶底物可用性改变的影响。由于营养环境直接影响宿主细胞的生理，我们的分析扩展到研究C。在基于哺乳动物间质液营养成分的新型生理培养基，间质液模型培养基（IFmM）中培养的哺乳动物宿主细胞中的贝氏体复制。基于IFmM的感染模型导致特定细胞系中CbΔpckA突变体表现出的复制缺陷加剧。CbΔpckA突变体在感染动物宿主期间也被减毒。总的来说，这项研究强调了造血能力有助于C。burnetii的嗜热性和C.在解决该病原体的毒力机制时，应考虑贝氏体。
Coxiella burnetii, the causative agent of query (Q) fever in humans, is an obligate intracellular bacterium. C. burnetii can naturally infect a broad range of host organisms (e.g., mammals and arthropods) and cell types. This amphotropic nature of C. burnetii, in combination with its ability to utilize both glycolytic and gluconeogenic carbon sources, suggests that the pathogen relies on metabolic plasticity to replicate in nutritionally diverse intracellular environments. To test the significance of metabolic plasticity in C. burnetii host cell colonization, C. burnetii intracellular replication in seven distinct cell lines was compared between a metabolically competent parental strain and a mutant, CbΔpckA, unable to undergo gluconeogenesis. Both the parental strain and CbΔpckA mutant exhibited host cell-dependent infection phenotypes, which were influenced by alterations to host glycolytic or gluconeogenic substrate availability. Because the nutritional environment directly impacts host cell physiology, our analysis was extended to investigate the response of C. burnetii replication in mammalian host cells cultivated in a novel physiological medium based on the nutrient composition of mammalian interstitial fluid, interstitial fluid-modeled medium (IFmM). An infection model based on IFmM resulted in exacerbation of a replication defect exhibited by the CbΔpckA mutant in specific cell lines. The CbΔpckA mutant was also attenuated during infection of an animal host. Overall, the study underscores that gluconeogenic capacity aids C. burnetii amphotropism and that the amphotropic nature of C. burnetii should be considered when resolving virulence mechanisms in this pathogen.
影响因子：
4.6
作者：
Reif KE;Ujczo JK;Alperin DC;Noh SM
通讯作者：
Noh SM