Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence.
Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence.
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Coxiella效应蛋白CvpF破坏RAB 26依赖性自噬以促进空泡生物发生和毒力。
DOI：
10.1080/15548627.2020.1728098
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发表时间：
2021-03
期刊：
影响因子：
13.3
通讯作者：
Martinez E
中科院分区：
文献类型：
--
作者：
Siadous FA;Cantet F;Van Schaik E;Burette M;Allombert J;Lakhani A;Bonaventure B;Goujon C;Samuel J;Bonazzi M;Martinez E
人畜共患病Q热的病原体贝氏柯克斯体在宿主细胞内的大空泡内复制，显示自溶酶体特征。该隔室的形成由细菌效应物介导，其干扰许多宿主膜运输途径。通过对Coxiella转座子突变体库的筛选，我们观察到cbu 0626中的转座子插入导致细胞内复制和液泡生物发生缺陷。在这里，我们证明CBU 0626是一个新的成员的柯克斯体空泡蛋白（CVP）家族的效应蛋白，这是易位的点/ICM分泌系统和本地化的囊泡与autolysosomal功能，以及柯克斯体空泡（CCV）。因此，我们将这种效应器重新命名为CvpF，即考克斯氏菌液泡蛋白F。CvpF特异性地与宿主小GT受体RAB 26相互作用，导致自噬体标记物MAP 1 LC 3B/LC 3B（微管相关蛋白1轻链3 β）募集至CCV。重要的是，在SCID小鼠感染模型中，与野生型细菌相比，cvpF：：Tn突变体高度减毒，突出了CvpF对柯克斯体毒力的重要性。这些结果表明，CvpF操纵内体运输和大自噬/自噬诱导，以获得最佳的C。贝氏菌液泡发生缩略语：ACCM：酸化柠檬酸半胱氨酸培养基;美联社：接头相关蛋白复合物; CCV：含基节的液泡; CVP：柯克斯体空泡蛋白; GDI：鸟苷核苷酸解离抑制剂; GDF：GDI解离因子; GEF：鸟嘌呤交换因子; LAMP 1：溶酶体相关膜蛋白1; MAP 1 LC 3B/LC 3B：微管相关蛋白1轻链3 β; MTORC 1：雷帕霉素激酶MTOR复合物1的机制靶标; PBS：磷酸盐缓冲盐水; PMA：佛波醇肉豆蔻酸酯乙酸酯; SQSTM 1/p62：多价螯合体1; WT：野生型。
Coxiella burnetii, the etiological agent of the zoonosis Q fever, replicates inside host cells within a large vacuole displaying autolysosomal characteristics. The development of this compartment is mediated by bacterial effectors, which interfere with a number of host membrane trafficking pathways. By screening a Coxiella transposon mutant library, we observed that transposon insertions in cbu0626 led to intracellular replication and vacuole biogenesis defects. Here, we demonstrate that CBU0626 is a novel member of the Coxiella vacuolar protein (Cvp) family of effector proteins, which is translocated by the Dot/Icm secretion system and localizes to vesicles with autolysosomal features as well as Coxiella-containing vacuoles (CCVs). We thus renamed this effector CvpF for Coxiella vacuolar protein F. CvpF specifically interacts with the host small GTPase RAB26, leading to the recruitment of the autophagosomal marker MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta) to CCVs. Importantly, cvpF::Tn mutants were highly attenuated compared to wild-type bacteria in the SCID mouse model of infection, highlighting the importance of CvpF for Coxiella virulence. These results suggest that CvpF manipulates endosomal trafficking and macroautophagy/autophagy induction for optimal C. burnetii vacuole biogenesis. Abbreviations: ACCM: acidified citrate cystein medium; AP: adaptor related protein complex; CCV: Coxiella-containing vacuole; Cvp: Coxiella vacuolar protein; GDI: guanosine nucleotide dissociation inhibitor; GDF: GDI dissociation factor; GEF: guanine exchange factor; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTORC1: mechanistic target of rapamycin kinase MTOR complex 1; PBS: phosphate-buffered saline; PMA: phorbol myristate acetate; SQSTM1/p62: sequestosome 1; WT: wild-type.
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影响因子：
6.7
作者：
Carey KL;Newton HJ;Lührmann A;Roy CR
通讯作者：
Roy CR
影响因子：
6.4
作者：
McDonough JA;Newton HJ;Klum S;Swiss R;Agaisse H;Roy CR
通讯作者：
Roy CR
影响因子：
4
作者：
Jin, Ramon U.;Mills, Jason C.
通讯作者：
Mills, Jason C.
影响因子：
6.7
作者：
Latomanski EA;Newton P;Khoo CA;Newton HJ
通讯作者：
Newton HJ
DOI：
10.1073/pnas.1309195110
发表时间：
2013-12-03
影响因子：
11.1
作者：
Larson, Charles L.;Beare, Paul A.;Heinzen, Robert A.
通讯作者：
Heinzen, Robert A.