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dc.contributor.authorPalace, Samantha G.
dc.contributor.authorProulx, Megan K.
dc.contributor.authorSzabady, Rose L.
dc.contributor.authorGoguen, Jon D.
dc.date2022-08-11T08:08:23.000
dc.date.accessioned2022-08-23T15:53:12Z
dc.date.available2022-08-23T15:53:12Z
dc.date.issued2018-04-28
dc.date.submitted2018-06-11
dc.identifier.citation<p>bioRxiv 310243; doi: https://doi.org/10.1101/310243. <a href="https://doi.org/10.1101/310243" target="_blank">Link to preprint on bioRxiv service.</a></p>
dc.identifier.doi10.1101/310243
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29305
dc.description.abstractVirulence of Yersinia pestis in mammals requires the type III secretion system, which delivers seven effector proteins into the cytoplasm of host cells to undermine immune responses. All seven of these effectors are conserved across Y. pestis strains, but three -- YopJ, YopT, and YpkA -- are apparently dispensable for virulence. Some degree of functional redundancy between effector proteins would explain both observations. Here, we use a combinatorial genetic approach to define the minimal subset of effectors required for full virulence in mice following subcutaneous infection. We found that a Y. pestis strain lacking YopJ, YopT, and YpkA is attenuated for virulence in mice, and that addition of any one of these effectors to this strain increases lethality significantly. YopJ, YopT, and YpkA likely contribute to virulence via distinct mechanisms. YopJ is uniquely able to cause macrophage cell death in vitro and to suppress accumulation of inflammatory cells to foci of bacterial growth in deep tissue, whereas YopT and YpkA cannot. The synthetic phenotypes that emerge when YopJ, YopT, and YpkA are removed in combination provide evidence that each enhances Y. pestis virulence, and that YopT and YpkA act through a mechanism distinct from that of YopJ.
dc.language.isoen_US
dc.relationNow published in Infection and Immunity doi: 10.1128/iai.00318-18
dc.rightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectmicrobiology
dc.subjectYersinia pestis
dc.subjecteffector proteins
dc.subjectYopJ
dc.subjectYopT
dc.subjectYpkA
dc.subjectmice
dc.subjectImmunology and Infectious Disease
dc.subjectMicrobiology
dc.titleGain of Function Analysis Reveals Non-Redundant Roles for the Yersinia pestis Type III Secretion System Effectors YopJ, YopT, and YpkA [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2536&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1531
dc.identifier.contextkey12290552
refterms.dateFOA2022-08-23T15:53:12Z
html.description.abstract<p>Virulence of <em>Yersinia pestis</em> in mammals requires the type III secretion system, which delivers seven effector proteins into the cytoplasm of host cells to undermine immune responses. All seven of these effectors are conserved across <em>Y. pestis</em> strains, but three -- YopJ, YopT, and YpkA -- are apparently dispensable for virulence. Some degree of functional redundancy between effector proteins would explain both observations. Here, we use a combinatorial genetic approach to define the minimal subset of effectors required for full virulence in mice following subcutaneous infection. We found that a <em>Y. pestis</em> strain lacking YopJ, YopT, and YpkA is attenuated for virulence in mice, and that addition of any one of these effectors to this strain increases lethality significantly. YopJ, YopT, and YpkA likely contribute to virulence via distinct mechanisms. YopJ is uniquely able to cause macrophage cell death <em>in vitro</em> and to suppress accumulation of inflammatory cells to foci of bacterial growth in deep tissue, whereas YopT and YpkA cannot. The synthetic phenotypes that emerge when YopJ, YopT, and YpkA are removed in combination provide evidence that each enhances <em>Y. pestis</em> virulence, and that YopT and YpkA act through a mechanism distinct from that of YopJ.</p>
dc.identifier.submissionpathfaculty_pubs/1531
dc.contributor.departmentDepartment of Microbiology and Physiological Systems


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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.