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Cell death induction facilitates egress of Coxiella burnetii from infected host cells at late stages of infection
Molecular Microbiology ( IF 2.6 ) Pub Date : 2023-12-19 , DOI: 10.1111/mmi.15210 Jan Schulze-Luehrmann 1 , Elisabeth Liebler-Tenorio 2 , Alfonso Felipe-López 1 , Anja Lührmann 1
Molecular Microbiology ( IF 2.6 ) Pub Date : 2023-12-19 , DOI: 10.1111/mmi.15210 Jan Schulze-Luehrmann 1 , Elisabeth Liebler-Tenorio 2 , Alfonso Felipe-López 1 , Anja Lührmann 1
Affiliation
Intracellular bacteria have evolved mechanisms to invade host cells, establish an intracellular niche that allows survival and replication, produce progeny, and exit the host cell after completion of the replication cycle to infect new target cells. Bacteria exit their host cell by (i) initiation of apoptosis, (ii) lytic cell death, and (iii) exocytosis. While bacterial egress is essential for bacterial spreading and, thus, pathogenesis, we currently lack information about egress mechanisms for the obligate intracellular pathogen C. burnetii, the causative agent of the zoonosis Q fever. Here, we demonstrate that C. burnetii inhibits host cell apoptosis early during infection, but induces and/or increases apoptosis at later stages of infection. Only at later stages of infection did we observe C. burnetii egress, which depends on previously established large bacteria-filled vacuoles and a functional intrinsic apoptotic cascade. The released bacteria are not enclosed by a host cell membrane and can infect and replicate in new target cells. In summary, our data argue that C. burnetii egress in a non-synchronous way at late stages of infection. Apoptosis-induction is important for C. burnetii egress, but other pathways most likely contribute.
中文翻译:
细胞死亡诱导促进伯氏柯克斯体在感染后期从受感染的宿主细胞中排出
细胞内细菌已经进化出侵入宿主细胞的机制,建立允许生存和复制的细胞内生态位,产生后代,并在复制周期完成后离开宿主细胞以感染新的靶细胞。细菌通过(i)启动细胞凋亡、(ii)裂解细胞死亡和(iii)胞吐作用离开宿主细胞。虽然细菌的流出对于细菌传播以及发病机制至关重要,但我们目前缺乏关于专性细胞内病原体伯内特念珠菌(人畜共患病Q热的病原体)的流出机制的信息。在这里,我们证明伯氏梭菌在感染早期抑制宿主细胞凋亡,但在感染后期诱导和/或增加细胞凋亡。仅在感染的后期阶段,我们才观察到伯内特念珠菌的出口,这取决于先前建立的充满细菌的大液泡和功能性内在凋亡级联。释放的细菌不被宿主细胞膜包围,可以感染新的靶细胞并在其中复制。总之,我们的数据表明,伯内特念珠菌在感染后期以非同步方式流出。细胞凋亡诱导对于伯氏梭菌的出口很重要,但其他途径也很可能有所贡献。
更新日期:2023-12-19
中文翻译:
细胞死亡诱导促进伯氏柯克斯体在感染后期从受感染的宿主细胞中排出
细胞内细菌已经进化出侵入宿主细胞的机制,建立允许生存和复制的细胞内生态位,产生后代,并在复制周期完成后离开宿主细胞以感染新的靶细胞。细菌通过(i)启动细胞凋亡、(ii)裂解细胞死亡和(iii)胞吐作用离开宿主细胞。虽然细菌的流出对于细菌传播以及发病机制至关重要,但我们目前缺乏关于专性细胞内病原体伯内特念珠菌(人畜共患病Q热的病原体)的流出机制的信息。在这里,我们证明伯氏梭菌在感染早期抑制宿主细胞凋亡,但在感染后期诱导和/或增加细胞凋亡。仅在感染的后期阶段,我们才观察到伯内特念珠菌的出口,这取决于先前建立的充满细菌的大液泡和功能性内在凋亡级联。释放的细菌不被宿主细胞膜包围,可以感染新的靶细胞并在其中复制。总之,我们的数据表明,伯内特念珠菌在感染后期以非同步方式流出。细胞凋亡诱导对于伯氏梭菌的出口很重要,但其他途径也很可能有所贡献。