State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, China.
J Bacteriol. 2021 Jul 22;203(16):e0050520. doi: 10.1128/JB.00505-20.
Edwardsiella piscicida is an intracellular pathogen within a broad spectrum of hosts. Essential to E. piscicida's virulence is its ability to invade and replicate inside host cells, yet the survival mechanisms and the nature of the replicative compartment remain unknown. Here, we characterized its intracellular lifestyle in nonphagocytic cells and showed that the intracellular replication of in nonphagocytic cells is dependent on its type III secretion system (T3SS) but not its type VI secretion system. Following internalization, is contained in vacuoles that transiently mature into early endosomes but subsequently bypasses the classical endosome pathway and fusion with lysosomes, which depend on its T3SS. Following rapid escape from the degradative pathway, was found to create a specialized replication-permissive niche characterized by endoplasmic reticulum (ER) markers. Furthermore, we found that a T3SS effector, EseJ, is responsible for the intracellular replication of by preventing endosome/lysosome fusion. experiments also confirmed that EseJ is necessary for bacterial colonization by in the epithelial layer, followed by systemic dissemination in both zebrafish and mice. Thus, this work elucidates the tactics used by to survive and proliferate within host nonphagocytic cells. is a facultative intracellular bacterium associated with septicemia and fatal infections in many animals, including fish and humans. However, little is known about its intracellular life, which is important for successful invasion of the host. The present study is the first comprehensive characterization of 's intracellular lifestyle in host cells. Upon internalization, is transiently contained in Rab5-positive vacuoles, but the pathogen prevents further endosome maturation and fusion with lysosomes by utilizing a T3SS effector, EseJ. In addition, the bacterium creates a specialized replication niche for rapid growth via an interaction with the ER. Our study provides new insights into the strategies used by to successfully establish an intracellular lifestyle that contributes to its survival and dissemination during infection.
爱德华氏菌是一种广泛宿主的胞内病原体。爱德华氏菌的毒力的关键在于其能够入侵和在宿主细胞内复制，但其生存机制和复制隔室的性质仍然未知。在这里，我们描述了它在非吞噬细胞中的胞内生活方式，并表明在非吞噬细胞中，爱德华氏菌的内复制依赖于其 III 型分泌系统（T3SS），而不是其 VI 型分泌系统。内化后，爱德华氏菌被包含在空泡中，这些空泡短暂成熟为早期内体，但随后绕过经典的内体途径和与溶酶体融合，这依赖于其 T3SS。在快速逃离降解途径后，发现爱德华氏菌创造了一个特殊的复制许可小生境，其特征是内质网（ER）标记。此外，我们发现 T3SS 效应物 EseJ 通过防止内体/溶酶体融合，负责爱德华氏菌的内复制。细菌定植实验也证实，EseJ 是爱德华氏菌在鱼类和小鼠上皮层定植和全身传播所必需的。因此，这项工作阐明了爱德华氏菌在宿主非吞噬细胞内生存和增殖所使用的策略。爱德华氏菌是一种兼性胞内菌，与许多动物（包括鱼类和人类）的败血症和致命感染有关。然而，对于其在细胞内的生活方式知之甚少，而这对于成功入侵宿主至关重要。本研究首次全面描述了爱德华氏菌在宿主细胞中的胞内生活方式。内化后，爱德华氏菌暂时被包含在 Rab5 阳性的空泡中，但该病原体通过利用 T3SS 效应物 EseJ 来阻止进一步的内体成熟和与溶酶体融合。此外，细菌通过与 ER 的相互作用为快速生长创造了一个特殊的复制小生境。我们的研究为爱德华氏菌成功建立胞内生活方式提供了新的见解，这种方式有助于其在感染过程中的生存和传播。
