Cellular and Developmental Biology of Coxiella burnetii

点击翻译按钮获取中文摘要

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.