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The\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            outer membrane Pla protease is essential for the development of pneumonic plague; however, the complete repertoire of substrates cleaved by Pla in the lungs is not known. In this study, we describe a proteomic screen to identify host proteins contained within the bronchoalveolar lavage fluid of mice that are cleaved and\/or processed by\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            in a Pla-dependent manner. We identified peroxiredoxin 6 (Prdx6), a host factor that contributes to pulmonary surfactant metabolism and lung defense against oxidative stress, as a previously unknown substrate of Pla. Pla cleaves Prdx6 at three distinct sites, and these cleavages disrupt both the peroxidase and phospholipase A\n            <jats:sub>2<\/jats:sub>\n            activities of Prdx6. In addition, we found that infection with wild-type\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            reduces the abundance of extracellular Prdx6 in the lungs compared to that after infection with \u0394\n            <jats:italic>pla<\/jats:italic>\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            , suggesting that Pla cleaves Prdx6 in the pulmonary compartment. However, following infection with either wild-type or \u0394\n            <jats:named-content content-type=\"genus-species\">pla Y. pestis<\/jats:named-content>\n            , Prdx6-deficient mice exhibit no differences in bacterial burden, host immune response, or lung damage from wild-type mice. Thus, while Pla is able to disrupt Prdx6 function\n            <jats:italic>in vitro<\/jats:italic>\n            and reduce Prdx6 levels\n            <jats:italic>in vivo<\/jats:italic>\n            , the cleavage of Prdx6 has little detectable impact on the progression or outcome of pneumonic plague.\n          <\/jats:p>","DOI":"10.1128\/iai.01168-15","type":"journal-article","created":{"date-parts":[[2015,11,10]],"date-time":"2015-11-10T03:58:26Z","timestamp":1447127906000},"page":"365-374","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Inactivation of Peroxiredoxin 6 by the Pla Protease of Yersinia pestis"],"prefix":"10.1128","volume":"84","author":[{"given":"Daniel L.","family":"Zimbler","sequence":"first","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin L.","family":"Eddy","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay A.","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4347-089X","authenticated-orcid":false,"given":"Wyndham W.","family":"Lathem","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2006.02.003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/249802"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2011.08.019"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2005"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2004.10.029"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00089409"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00131"},{"key":"e_1_3_3_9_2","first-page":"153","article-title":"Antimicrobial peptides in the airway","volume":"306","author":"Laube DM","year":"2006","unstructured":"Laube DM, Yim S, Ryan LK, Kisich KO, Diamond G. 2006. 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