The role of the central region of YopD in Yersinia pseudotuberculosis virulence (P3144)

Abstract

Abstract Human pathogenic Yersinia express a type III secretion system (T3SS) critical for virulence. The T3SS proteins YopD and YopB form pores in host membranes and mediate injection of effector proteins inside host cells to disrupt innate immune defenses such as production of reactive oxygen species (ROS). Discrete functional domains within YopD have been identified, yet the YopD central region (amino acids 150-227) remains largely uncharacterized. We assessed the importance of the YopD central region by generating Y. pseudotuberculosis YopDΔ150-170 and YopDΔ207-227 mutants and analyzing their virulence in mouse infection models. Y. pseudotuberculosis YopDΔ150-170 and YopDΔ207-227 grew normally in mesenteric lymph nodes and Peyer’s patches following oral infection, but displayed a 20-29,000-fold defect in the spleen and liver. These mutants were also highly attenuated following intraperitoneal infection. These data indicate that the YopD150-227 central region is critical for Y. pseudotuberculosis disseminated infection. To identify the underlying cause of this virulence defect, we examined the ability of the YopDΔ150-170 and YopDΔ207-227 mutants to translocate T3SS cargo and inhibit ROS production in macrophages. While only the YopDΔ150-170 mutant exhibited translocation defects, both mutants failed to fully inhibit ROS production. We hypothesize that the YopD central region facilitates optimal T3SS effector protein delivery to effectively disarm innate immune defenses.