Cellular and Developmental Biology of Coxiella burnetii

伯内氏柯克斯体的细胞和发育生物学

• 批准号: 6809424
• 负责人: Robert A Heinzen
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6809424
• 关键词: Coxiella burnetii; Q fever; bacteria infection mechanism; biological signal transduction; bioterrorism /chemical warfare; cell biology; cell differentiation; cell morphology; confocal scanning microscopy; fluorescence microscopy; mass spectrometry; microarray technology; tissue /cell culture; vesicle /vacuole

Coxiella burnetii is an obligate intracellular bacterium and the causative agent of the zoonosis human Q (query) fever. Acute Q fever normally manifests as a self-limiting influenza-like illness. Rare but serious chronic infections can occur that usually present as endocarditis or hepatitis. The vast majority of human Q fever cases are acquired though contact with infected domestic livestock where the organism can be endemic. C. burnetii can chronically infect a variety of animals and is shed in large numbers in various secretions and products of parturition. Adding to the insidious nature of the organism is an infective dose approaching one organism and a remarkable extracellular stability approaching that of a bacterial spore. Environmental resistance also correlates with resistance to the degradative conditions of a phagolysosomal-like parasitophorous vacuole (PV), Coxiella's niche within host macrophages. The impressive environmental stability of C. burnetii is likely due to the biogenesis of a highly resistant cell form termed the small cell variant (SCV). This form arises during a biphasic developmental cycle and is likely responsible for the majority of environmentally acquired cases of Q fever. Once internalized and sequestered in a PV, SCV morphologically differentiate into more metabolically and replicatively active large cell variants (LCV). Mature PV contain a mixture of SCV, LCV and intermediate forms. The molecular biology of C. burnetii morphological differentiation is poorly understood. Important areas of future investigation include identification of the cellular conditions and signal transduction that drive development, the kinetics of development, the relative infectivity of SCV and LCV for various hosts, the transcriptional and translational capabilities of cell forms, and the biochemical composition of SCV and LCV that confer their unique biological properties. The lysosomal-like PV of C. burnetii is unique among intracellular bacteria. In all cases examined, invasive bacteria modify their PV to enhance survival and usually growth. Bacterial effectors of PV remodeling generally interact with host molecules that regulate vesicular trafficking. The nature and extent of modification of the C. burnetii PV is unknown. Coxiella contains a near compete copy of the type IV secretion apparatus genes of Legionella pneumophila, a phylogenetically close relative. Because Legionella requires functional type IV secretion to establish its replicative niche, it is logical to assume a similar requirement for Coxiella.

Coxiella burnetii是一种强制性细胞内细菌，也是人动物病Q（Query）发烧的病因。急性Q发烧通常表现为一种自限的流感样疾病。通常会出现罕见但严重的慢性感染，通常会出现心内膜炎或肝炎。绝大多数人类Q发烧病例是通过与感染的家庭牲畜接触的，那里的生物可能是地方性的。 C. burnetii可以长期感染各种动物，并在各种分泌物和分娩产物中大量脱落。加上生物体的阴险性质是一种感染剂量，接近一种生物体，而细胞外稳定性接近细菌孢子的剂量。环境抗性还与对吞噬性寄生虫样的寄生虫果实（PV）的降解条件的抗性，Coxiella在宿主巨噬细胞中的利基市场相关。 C. burnetii的令人印象深刻的环境稳定性可能是由于称为小细胞变体（SCV）的高度抗性细胞形式的生物发生。这种形式是在双相发育周期中产生的，很可能是大多数环保Q发烧案件的原因。一旦内化并在PV中进行了隔离，SCV在形态上会分化为更代谢和复制的大细胞变异（LCV）。成熟的PV包含SCV，LCV和中间形式的混合物。 C. burnetii形态学分化的分子生物学知之甚少。未来研究的重要领域包括鉴定驱动发育的细胞条件和信号转导，开发动力学，各种宿主的SCV和LCV的相对感染性，细胞形式的转录和翻译能力以及SCV和LCV的生物化学组成，从而赋予其独特的生物学特性。 C. burnetii的溶酶体样PV在细胞内细菌中是独一无二的。在所有检查的情况下，侵入性细菌都会改变其PV，以增强生存和生长。 PV重塑的细菌效应子通常与调节囊泡运输的宿主分子相互作用。 C. burnetii PV的修饰的性质和程度尚不清楚。 Coxiella包含一个近IIV型分泌型肺炎军团菌的近乎竞争的副本，这是一种系统发育近亲。由于Legionella需要IV型功能性分泌才能建立其复制性位，因此合理地假设对Coxiella的要求是合乎逻辑的。