Research
| Title： | The Edwardsiella T3SS effector EseQ promotes invasion by altering the cell's cytoskeleton and disrupting the epithelial barrier |
|---|---|
| First author： | Jiang, Xiu Long; He, Tian Tian; Tang, Pu Yu; Wang, Qin; Nie, Pin; Xie, Hai Xia |
| Journal： | MSPHERE |
| Years： | 2025 |
| DOI： | 10.1128/msphere.00520-25 |
| Abstract： | Edwardsiella piscicida is a Gram-negative, intracellular, enteric pathogen that primarily causes hemorrhagic septicemia in fish. It survives and replicates within host cells by delivering a subset of effector proteins via the type III secretion system (T3SS). Previous research has identified a novel T3SS effector, EseQ, in E. piscicida; however, its function remains unclear. This study reveals that EseQ binds to both alpha-tubulin and GEF-H1 (Rho guanine nucleotide exchange factor 1), causing microtubule destabilization and the release of activated GEF-H1. Active GEF-H1 then stimulates the conversion of GDP-RhoA (the inactive form) to GTP-RhoA (the active form), which subsequently induces stress fiber formation in a ROCK-dependent manner. Stress fibers induced by EseQ alter the architecture of zonula occludens-1-mediated intercellular junctions. This leads to increased permeability of the epithelial barrier, thereby facilitating the translocation of E. piscicida through epithelial cell layers and its invasion into zebrafish larvae. In conclusion, this study demonstrates that the Edwardsiella T3SS effector protein EseQ promotes invasion by manipulating the microtubule and actin cytoskeletons and by disrupting the epithelial barrier.IMPORTANCEEdwardsiella piscicida causes severe hemorrhagic septicemia in marine and freshwater fish worldwide, resulting in significant economic losses for the aquaculture industry (K. Y. Leung, Q. Wang, Z. Yang, and B. A. Siame, Virulence 10:555-567, 2019, https://doi.org/10.1080/21505594.2019.1621648). Our previous research identified a novel type III secretion system effector, EseQ, in E. piscicida whose function remains to be elucidated. In this work, we showed that EseQ binds to tubulin and GEF-H1 and destabilizes microtubules. GEF-H1 released from microtubules activates the RhoA-ROCK-MLCII signaling pathway, leading to stress fiber formation in epithelial cells. EseQ deforms the epithelial barrier and promotes E. piscicida's invasion in a stress fiber-dependent manner. This work contributes to the understanding of the mechanism by which E. piscicida invades host cells. |
