Genetics of Coxiella burnetii

伯纳蒂克希菌是一种专性细胞内细菌，是人Q （query）热人畜共患病的病原体。急性Q热通常表现为一种自限性流感样疾病。罕见但严重的慢性感染可发生，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而获得的，在这些家畜中，这种生物可能是地方性的。伯氏原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传播。增加了有机体的阴险本质是一个感染剂量接近一个有机体和一个显着的细胞外稳定性接近细菌孢子。环境抗性还与对吞噬溶酶体样寄生液泡（PV）降解条件的抗性相关，PV是宿主巨噬细胞内的Coxiella生态位。

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.