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Type III secretion system protein EspA (EspA) is a critical structural component of the Type III secretion system (T3SS) found in attaching and effacing (A/E) bacterial pathogens, such as enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli [1, 4]. EspA subunits polymerize to form a large, filamentous appendage that extends from the bacterial needle complex to the host cell membrane, serving as an essential conduit for the translocation of virulence effectors [3, 10]. These effectors subvert host cellular processes, leading to actin pedestal formation and the characteristic intestinal lesions that cause severe diarrhea and hemolytic uremic syndrome [2, 9]. Due to its indispensable role in the infection process and its accessible extracellular location, EspA is a major target for anti-virulence strategies [14, 15]. Therapeutic approaches under development include recombinant protein vaccines and neutralizing monoclonal antibodies designed to disrupt the T3SS bridge, as well as small-molecule inhibitors that target the assembly of the secretion machinery [7, 24, 30].
Inhibition of Type III secretion system (T3SS) filament assembly and blocking of the translocation conduit to prevent the delivery of virulence effector proteins into host cells.
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