YopE

YopE is a virulence factor produced by pathogenic Yersinia species, including Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica. It is an effector protein delivered into host cells by the bacteria’s type III secretion system, a needle-like apparatus used to inject proteins directly into the cytosol of target cells during infection.

Once inside the host cell, YopE functions as a Rho GTPase-activating protein (GAP). It targets members of the Rho family of small GTPases, such as Rac and Cdc42, stimulating their GTP hydrolysis and locking them in an inactive GDP-bound state. This leads to disruption of the actin cytoskeleton and impairment of actin-dependent processes, including phagocytosis by macrophages and other immune cells, thereby promoting bacterial survival and initial establishment of infection.

Delivery and regulation: YopE is translocated into host cells via the type III secretion apparatus upon contact with the host. Its expression and secretion are regulated by environmental signals, including temperature and calcium levels; expression is typically upregulated at mammalian body temperature and in conditions that mimic the intracellular environment, with transcriptional control involving regulators such as LcrF.

Role in virulence: YopE contributes to virulence by inhibiting phagocytic uptake and altering host cell signaling. It functions alongside other Yersinia Yop effectors, such as YopH, YopJ, and YopM, in a coordinated strategy to undermine host defenses. In animal models, the presence of YopE enhances bacterial survival and dissemination, though virulence usually arises from the combined action of multiple effectors.

Genetics and study: YopE is encoded within yop operons on virulence plasmids common to pathogenic Yersinia. It has been the subject of structural and functional studies aimed at elucidating the GAP domain and the molecular interfaces with Rho GTPases, informing broader understanding of host-pathogen interactions.