{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:32:21Z","timestamp":1791340341060,"version":"4.3.1"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,2,8]],"date-time":"2014-02-08T00:00:00Z","timestamp":1391817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2014,3]]},"abstract":"Summary<\/jats:title>F<\/jats:italic><\/jats:styled-content>rancisella tularensis<\/jats:italic> is a category A<\/jats:styled-content> biodefence agent that causes a fatal human disease known as tularaemia. The pathogenicity of F<\/jats:italic><\/jats:styled-content>.\u2009tularensis<\/jats:italic> depends on its ability to persist inside host immune cells primarily by resisting an attack from host\u2010generated reactive oxygen and nitrogen species (ROS<\/jats:styled-content>\/RNS<\/jats:styled-content>). Based on the ability of F<\/jats:italic><\/jats:styled-content>.\u2009tularensis<\/jats:italic> to resist high ROS<\/jats:styled-content>\/RNS<\/jats:styled-content> levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defences to render ROS<\/jats:styled-content> resistance. By screening a transposon insertion library of F<\/jats:italic><\/jats:styled-content>.\u2009tularensis<\/jats:italic>\u2005LVS<\/jats:styled-content> in the presence of hydrogen peroxide, we have identified an oxidant\u2010sensitive mutant in putative EmrA<\/jats:styled-content>1 (FTL<\/jats:styled-content>_0687) secretion protein. The results demonstrate that the emrA1<\/jats:italic><\/jats:styled-content> mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild\u2010type F<\/jats:italic><\/jats:styled-content>.\u2009tularensis<\/jats:italic>\u2005LVS<\/jats:styled-content> levels by either transcomplementation, inhibition of ROS<\/jats:styled-content> generation or infection in NADPH<\/jats:styled-content> oxidase deficient (gp91Phox<\/jats:italic><\/jats:styled-content>\u2212\/\u2212<\/jats:sup>) macrophages. The emrA1<\/jats:italic><\/jats:styled-content> mutant is attenuated for virulence, which is restored by infection in gp91Phox<\/jats:italic><\/jats:styled-content>\u2212\/\u2212<\/jats:sup> mice. Further, EmrA<\/jats:styled-content>1 contributes to oxidative stress resistance by affecting secretion of F<\/jats:italic><\/jats:styled-content>rancisella<\/jats:italic> antioxidant enzymes SodB<\/jats:styled-content> and KatG<\/jats:styled-content>. This study exposes unique links between transporter activity and the antioxidant defence mechanisms of F<\/jats:italic><\/jats:styled-content>.\u2009tularensis<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/mmi.12509","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T06:14:40Z","timestamp":1389161680000},"page":"976-995","source":"Crossref","is-referenced-by-count":36,"title":["EmrA<\/scp>1 membrane fusion protein of F<\/i><\/scp>rancisella tularensis<\/i>\u2005LVS<\/scp> is required for resistance to oxidative stress, intramacrophage survival and virulence in mice"],"prefix":"10.1111","volume":"91","author":[{"given":"Zhuo","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Basic and Social Sciences Albany College of Pharmacy and Health Sciences Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukalyani","family":"Banik","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology New York Medical College Valhalla New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshita","family":"Rane","sequence":"additional","affiliation":[{"name":"Department of Basic and Social Sciences Albany College of Pharmacy and Health Sciences Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa T.","family":"Mora","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology New York Medical College Valhalla New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seham M.","family":"Rabadi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology New York Medical College Valhalla New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Department of Molecular Genetics and Microbiology Stony Brook University Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Thanassi","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Department of Molecular Genetics and Microbiology Stony Brook University Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra Shekhar","family":"Bakshi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology New York Medical College Valhalla New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Basic and Social Sciences Albany College of Pharmacy and Health Sciences Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2003.09.011"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00544.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2005.12.004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00266-06"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.07.051"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2005"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2007.01033.x"},{"key":"e_1_2_6_9_1","first-page":"1126","article-title":"[Tularemia, a potential bioterrorism weapon]","volume":"32","author":"Bossi P.","year":"2003","journal-title":"Presse Med"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03438.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.04.034"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.96"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.21.2763"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01012-10"},{"key":"e_1_2_6_15_1","unstructured":"Federal Register(2012)Possession use and transfer of select agents and toxins; Biennial review Final rule. 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