ABSTRACT

Coxiella burnetii is an obligate intracellular bacterium that causes the human disease Q fever, which can manifest as an acute flu-like illness or a long-term chronic illness, such as endocarditis. Three genotypes (ST8, ST16, and ST20) of Coxiella burnetii are commonly found in the contemporary US and are associated with specific animal hosts. Although all three genotypes have been isolated from humans with Q fever, studies comparing virulence between C. burnetii sequence types have been rare. Here, groups of mice were infected via aerosol inoculation with isolates derived from cow’s milk, environmental, animal, and human samples. Mice were monitored for weight loss and blood samples were takenweekly. Animals were euthanized at 2- and 12-weeks post-infection, and bacterial burden was determined for tissues by real-time PCR. The levels of anti-Coxiella antibodies and selected inflammatory cytokines were determined for serum samples. Weight loss and splenomegaly were observed in mice infected with ST20 and ST16 isolates but were absent in the mice infected with ST8 isolates. Bacterial concentrations in the tissues were lower in the ST8 isolates at 2 weeks post-infection relative to all other isolates. ST16 and ST20 isolates induced robust antibody and cytokine responses, while ST8 isolates produced significantly lower anti-C. burnetii titers early in the infection but saw increased titers in some animals several weeks post-infection. The data suggest that the ST8 isolates are less virulent in this mouse model, as they produce less robust antibody responses that are slow to develop, relative to the ST16 and ST20 isolates.

摘要

Coxiella burnetii是一种专性细胞内细菌，可导致人类疾病 Q 热，可表现为急性流感样疾病或长期慢性疾病，如心内膜炎。Coxiella burnetii的三种基因型（ST8、ST16 和 ST20）在当代美国很常见，并且与特定的动物宿主有关。尽管所有三种基因型均已从 Q 热人类中分离出来，但研究比较了C. burnetii之间的毒力序列类型很少见。在这里，一组小鼠通过气溶胶接种从牛奶、环境、动物和人类样本中提取的分离物进行感染。监测小鼠的体重减轻并且每周采集血样。在感染后 2 周和 12 周对动物实施安乐死，并通过实时 PCR 测定组织的细菌负荷。测定血清样品的抗 Coxiella 抗体和选定的炎性细胞因子的水平。在感染 ST20 和 ST16 分离株的小鼠中观察到体重减轻和脾肿大，但在感染 ST8 分离株的小鼠中不存在。与所有其他分离株相比，ST8 分离株在感染后 2 周时组织中的细菌浓度较低。ST16 和 ST20 分离株诱导强烈的抗体和细胞因子反应，C. burnetii在感染早期滴度，但在感染后数周某些动物的滴度增加。数据表明，与 ST16 和 ST20 分离株相比，ST8 分离株在该小鼠模型中的毒性较低，因为它们产生的抗体反应较弱且发展缓慢。