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With the pipeline for new antibiotics virtually empty, there is an urgent need to develop novel therapeutics. Bacteria require iron to establish infection, and specialized pathogen-associated iron acquisition systems like yersiniabactin, common among pathogenic species in the family<jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>, including multidrug-resistant<jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>and pathogenic<jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>, represent potentially novel therapeutic targets. Although the yersiniabactin system was recently identified as a vaccine target for uropathogenic<jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>(UPEC)-mediated urinary tract infection (UTI), its contribution to UPEC pathogenesis is unknown. Using an<jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>mutant (strain 536\u0394<jats:italic>fyuA<\/jats:italic>) unable to acquire yersiniabactin during infection, we established the yersiniabactin receptor as a UPEC virulence factor during cystitis and pyelonephritis, a fitness factor during bacteremia, and a surface-accessible target of the experimental FyuA vaccine. In addition, we determined through transcriptome sequencing (RNA-seq) analyses of RNA from<jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>causing cystitis in women that iron acquisition systems, including the yersiniabactin system, are highly expressed by bacteria during natural uncomplicated UTI. Given that yersiniabactin contributes to the virulence of several pathogenic species in the family<jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>, including UPEC, and is frequently associated with multidrug-resistant strains, it represents a promising novel target to combat antibiotic-resistant infections.<\/jats:p>","DOI":"10.1128\/iai.02904-14","type":"journal-article","created":{"date-parts":[[2015,1,27]],"date-time":"2015-01-27T02:33:40Z","timestamp":1422326020000},"page":"1443-1450","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["Blocking Yersiniabactin Import Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and Represents a Novel Target To Prevent Urinary Tract Infection"],"prefix":"10.1128","volume":"83","author":[{"given":"Ariel R.","family":"Brumbaugh","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara N.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sargurunathan","family":"Subashchandrabose","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie D.","family":"Himpsl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy H.","family":"Hazen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Rasko","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L. 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