Genetics of Coxiella burnetii

伯内氏柯克斯体的遗传学

• 批准号: 6987135
• 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/6987135
• 关键词: Coxiella burnetii; Q fever; bacteria infection mechanism; bacterial genetics; bioterrorism /chemical warfare; confocal scanning microscopy; disease /disorder classification; functional /structural genomics; genetic polymorphism; genetic strain; genetic transcription; microarray technology; microorganism classification; molecular cloning; polymerase chain reaction; proteomics; virulence

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 presents 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 phagolysosome-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. An important area of future research includes defining the transcriptional capabilities of cell forms and the response of C. burnetii to lysosomal stress. Restriction fragment-length polymorphism analysis reveals considerable genomic DNA heterogeneity among C. burnetii strains. Moreover, strains can be grouped according to an association with human acute or chronic disease, suggesting that groups have unique virulence potential. Although the severity of disease and the potential for chronicity may involve patient factors, there is a clear association of C. burnetii isolates with disease outcome. The extent and biological relevance of strain variation is unknown. Strains of lower virulence may result in subclinical infections where diagnosis and treatment are delayed, resulting in chronic infections with serious consequence years or decades later. Genetic systems such as complementation, transposon mutagenesis, and allelic exchange are invaluable tools in the study of bacterial virulence. These methods require the introduction of foreign DNA into the bacterial recipient usually via electroporation. Genetic transformation generally requires strong selectable markers in the form of antibiotic resistance genes. While genetic transformation has been described for C. burnetii, the system is hampered by inadequate antibiotic selection, instability of introduced DNA, and the lack of efficient cloning methods for clonal isolation.

贝氏柯克斯体是一种专性胞内细菌，是人畜共患Q热的病原体。急性Q热通常表现为自限性流感样疾病。罕见但严重的慢性感染可能会发生，通常表现为心内膜炎或肝炎。绝大多数人类Q热病例是通过接触受感染的家畜获得的，在家畜中，这种生物体可能是地方性的。C.贝氏体可慢性感染多种动物，并在各种分泌物和分娩产物中大量脱落。增加了生物体的潜伏性质是接近一个生物体的感染剂量和接近细菌孢子的显著胞外稳定性。环境抗性也与对吞噬溶酶体样寄生虫空泡（PV）的降解条件的抗性相关，PV是宿主巨噬细胞内的柯克斯体的生态位。 C.贝氏体的感染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。这种形式出现在一个双相发育周期，并可能负责大多数环境获得性Q热病例。一旦在PV中内化和隔离，SCV在形态上分化成代谢和复制活性更高的大细胞变体（LCV）。成熟PV含有SCV、LCV和中间形式的混合物。对C.贝氏体的形态分化知之甚少。未来研究的一个重要领域包括确定细胞形式的转录能力和C。burnetii的溶酶体应激。 限制性片段长度多态性分析揭示了C. Burnetii菌株此外，菌株可以根据与人类急性或慢性疾病的相关性进行分组，这表明这些群体具有独特的毒力潜力。虽然疾病的严重程度和慢性化的可能性可能涉及患者因素，但C。贝氏分离物与疾病结果。菌株变异的程度和生物学相关性尚不清楚。较低毒力的菌株可能导致亚临床感染，延误诊断和治疗，导致数年或数十年后的严重后果的慢性感染。 遗传系统如互补、转座子诱变和等位基因交换是研究细菌毒力的宝贵工具。这些方法通常需要通过电穿孔将外源DNA引入细菌受体。遗传转化通常需要抗生素抗性基因形式的强选择标记。虽然已经描述了C.在Burnetii中，该系统受到抗生素选择不足、引入的DNA不稳定以及缺乏用于克隆分离的有效克隆方法的阻碍。