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The adverse effects of<jats:italic>Yersinia pestis<\/jats:italic>, the causative agent of plague, were examined by infecting J774A.1 cells, RAW264.7 cells, and primary murine macrophages with the EV76 strain and with the fully virulent Kimberley53 strain.<jats:italic>Y. pestis<\/jats:italic>exerts YopJ-dependent suppression of tumor necrosis factor alpha secretion and phosphorylation of mitogen-activated protein kinases and thus resembles enteropathogenic<jats:italic>Yersinia<\/jats:italic>. However,<jats:italic>Y. pestis<\/jats:italic>is less able to activate caspases, to suppress NF-\u03baB activation, and to induce apoptosis in macrophages than the high-virulence<jats:italic>Y. enterocolitica<\/jats:italic>WA O:8 strain. These differences appear to be related to lower efficiency of YopJ effector translocation by<jats:italic>Y. pestis<\/jats:italic>. The efficiencies of effector translocation and of apoptosis induction can be enhanced either by using a high bacterial load in a synchronized infection or by overexpressing exogenous YopJ in<jats:italic>Y. pestis<\/jats:italic>. Replacing YopJ with the homologous<jats:italic>Y. enterocolitica<\/jats:italic>effector YopP can further enhance these effects. Overexpression of YopP in a<jats:italic>yopJ<\/jats:italic>-deleted<jats:italic>Y. pestis<\/jats:italic>background leads to rapid and effective translocation into target cells, providing<jats:italic>Y. pestis<\/jats:italic>with the high cytotoxic potential of<jats:italic>Y. enterocolitica<\/jats:italic>WA O:8. We suggest that the relative inferiority of<jats:italic>Y. pestis<\/jats:italic>in triggering cell death in macrophages may be advantageous for its in vivo propagation in the early stages of infection.<\/jats:p>","DOI":"10.1128\/iai.00097-06","type":"journal-article","created":{"date-parts":[[2006,5,19]],"date-time":"2006-05-19T23:52:41Z","timestamp":1148082761000},"page":"3239-3250","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":60,"title":["Interaction of<i>Yersinia pestis<\/i>with Macrophages: Limitations in YopJ-Dependent Apoptosis"],"prefix":"10.1128","volume":"74","author":[{"given":"Ayelet","family":"Zauberman","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P.O. 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