type III secretion system effector EseG modulates cytoskeletal dynamics and immune response in macrophages.

is a gram-negative enteric pathogen responsible for enteric septicemia of catfish. One of the critical virulence factors identified in is its type III secretion system (T3SS). In this study, we report that the T3SS effector protein EseG requires the small chaperone protein EscB for translocation. EseG shows partial homology to two T3SS effectors, SseG and SseF, as well as to the effector EseG, all of which also require chaperones for translocation. Functionally, EseG interacts with and inactivates Ras homolog family member A (RhoA), a small GTPase that regulates the dynamic organization of the microtubule and actin cytoskeleton. The cytoskeleton is vital for cell morphology, polarity, adhesion, exocytosis, endocytosis, cytokinesis, and transcriptional control. We demonstrate that inactivation of RhoA by EseG leads to the disassembly of both the microtubule and actin cytoskeleton. Moreover, EseG was found to modulate immune responses by altering the expression of several pro-inflammatory interleukins and transcription factors, as well as cyclooxygenase-2 (COX-2). Reduced expression of COX-2 leads to decreased production of prostaglandin E2, a key mediator of inflammation. Additionally, a Δ mutant strain exhibited reduced virulence and persistence in channel catfish (), underscoring the importance of EseG in the disease process. Collectively, our data highlight EseG as a critical factor in pathogenesis, particularly in its ability to modulate host immune responses. By elucidating the function of EseG, this study contributes to a deeper understanding of pathogenesis.