Contribution of the Major Secreted Yops of Yersinia enterocolitica O:8 to Pathogenicity in the Mouse Infection Model

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Abstract
Pathogenic yersiniae ( Yersinia pestis , Y. pseudotuberculosis , and Y. enterocolitica ) harbor a 70-kb virulence plasmid (pYV) that encodes a type III secretion system and a set of at least six effector proteins (YopH, YopO, YopP, YopE, YopM, and YopT) that are injected into the host cell cytoplasm. Yops ( Yersinia outer proteins) disturb the dynamics of the cytoskeleton, inhibit phagocytosis by macrophages, and downregulate the production of proinflammatory cytokines, which makes it possible for yersiniae to multiply extracellularly in lymphoid tissue. Y. enterocolitica serotype O:8 belongs to the highly mouse-pathogenic group of yersiniae in contrast to Y. enterocolitica serotype O:9. However, there has been no systematic study of the contribution of Yops to the pathogenicity of Y. enterocolitica O:8 in mice. We generated a set of yop gene deletion mutants of Y. enterocolitica O:8 by using the novel Red cloning procedure. We subsequently analyzed the contribution of yopH , -O , -P , -E , -M , -T , and - Q deletions to pathogenicity after oral and intravenous infection of mice. Here we showed for the first time that a Δ yopT deletion mutant colonizes mouse tissues to a greater extent than the parental strain. The Δ yopO , Δ yopP , and Δ yopE mutants were only slightly attenuated after oral infection since they were still able to colonize the spleen and liver and cause systemic infection. The Δ yopO mutant was lethal for mice, whereas ΔyopP and Δ yopE mutants were successfully eliminated from the spleen and liver 2 weeks after infection. In contrast the Δ yopH , Δ yopM , and Δ yopQ mutants were highly attenuated and not able to colonize the spleen and liver on any of the days tested. The Δ yopH , Δ yopO , Δ yopP , Δ yopE , Δ yopM , and Δ yopQ mutants had only modest defects in the colonization of the small intestine and Peyer's patches. The Δ yopE mutant was eliminated from the small intestine 3 weeks after infection, whereas the Δ yopH , ΔyopP , ΔyopM , and ΔyopQ mutants continued to colonize the small intestine at this time.