Coxiella burnetii Plasmid Effector B Promotes LC3-II Accumulation and Contributes To Bacterial Virulence in a SCID Mouse Model
Coxiella burnetii Plasmid Effector B Promotes LC3-II Accumulation and Contributes To Bacterial Virulence in a SCID Mouse Model
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DOI：
10.1128/iai.00016-22
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发表时间：
2022-05-19
影响因子：
3.1
通讯作者：
Xiong, Xiaolu
中科院分区：
文献类型：
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作者：
Fu, Mengjiao;Zhang, Jianing;Xiong, Xiaolu
布氏柯克斯体是人畜共患Q热的病原体，其特征是在宿主细胞内溶酶体衍生的含柯克斯体的空泡（CCV）内复制。C.据报道，bumetii参与操纵自噬以促进CCV的发展和细菌复制。在此，我们发现Coxiella质粒效应子B（Cpe B）定位于由LC 3和LAMP 1靶向的液泡膜上，并促进LC 3-II积累。与此同时，C.缺乏QpH 1质粒的贝氏菌株诱导较少的LC 3-II积累，这伴随着较小的CCV和THP-1细胞中较低的细菌负荷。在缺乏QpH 1的菌株中表达CpeB导致LC 3-II积累的恢复，但对较小的CCV表型没有影响。在严重联合免疫缺陷（SOD）小鼠模型中，感染表达CpeB的菌株导致脾脏和肝脏中的细菌负荷显著高于其缺乏QpH 1的亲本菌株。我们还发现CpeB靶向Rab 11 a以促进LC 3-II积累。肠内接种C.在Rab 11 a条件性基因敲除（Rab 11 a（-/-）CKO）小鼠中，贝氏杆菌导致较低的细菌负荷和较轻的肺部病变。总的来说，这些结果表明，CpeB促进C。通过涉及Rab 11 a的途径诱导LC 3-II的积累来增强贝氏体的毒力。
Coxiella bumetii, the causative agent of zoonotic Q fever, is characterized by replicating inside the lysosome-derived Coxiella-containing vacuole (CCV) in host cells. Some effector proteins secreted by C. bumetii have been reported to be involved in the manipulation of autophagy to facilitate the development of CCVs and bacterial replication. Here, we found that the Coxiella plasmid effector B (CpeB) localizes on vacuole membrane targeted by LC3 and LAMP1 and promotes LC3-II accumulation. Meanwhile, the C. burnetii strain lacking the QpH1 plasmid induced less LC3-II accumulation, which was accompanied by smaller CCVs and lower bacterial loads in THP-1 cells. Expression of CpeB in the strain lacking QpH1 led to restoration in LC3-II accumulation but had no effect on the smaller CCV phenotype. In the severe combined immune deficiency (SOD) mouse model, infections with the strain expressing CpeB led to significantly higher bacterial burdens in the spleen and liver than its parent strain devoid of QpH1. We also found that CpeB targets Rabl la to promote LC3-II accumulation. Intratracheally inoculated C. burnetii resulted in lower bacterial burdens and milder lung lesions in Rab11a conditional knockout (Rab11a(-/-) CKO) mice. Collectively, these results suggest that CpeB promotes C. burnetii virulence by inducing LC3-II accumulation via a pathway involving Rab11a.