{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:04:17Z","timestamp":1792260257262,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009314","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000}}],"reference-count":93,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Type 1 pili have long been considered the major virulence factor enabling colonization of the urinary bladder by uropathogenic<jats:italic>Escherichia coli<\/jats:italic>(UPEC). The molecular pathogenesis of pyelonephritis is less well characterized, due to previous limitations in preclinical modeling of kidney infection. Here, we demonstrate in a recently developed mouse model that beyond bladder infection, type 1 pili also are critical for establishment of ascending pyelonephritis. Bacterial mutants lacking the type 1 pilus adhesin (FimH) were unable to establish kidney infection in male C3H\/HeN mice. We developed an<jats:italic>in vitro<\/jats:italic>model of FimH-dependent UPEC binding to renal collecting duct cells, and performed a CRISPR screen in these cells, identifying desmoglein-2 as a primary renal epithelial receptor for FimH. The mannosylated extracellular domain of human DSG2 bound directly to the lectin domain of FimH<jats:italic>in vitro<\/jats:italic>, and introduction of a mutation in the FimH mannose-binding pocket abolished binding to DSG2. In infected C3H\/HeN mice, type 1-piliated UPEC and Dsg2 were co-localized within collecting ducts, and administration of mannoside FIM1033, a potent small-molecule inhibitor of FimH, significantly attenuated bacterial loads in pyelonephritis. Our results broaden the biological importance of FimH, specify the first renal FimH receptor, and indicate that FimH-targeted therapeutics will also have application in pyelonephritis.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009314","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T18:41:18Z","timestamp":1611945678000},"page":"e1009314","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":44,"title":["A host receptor enables type 1 pilus-mediated pathogenesis of Escherichia coli pyelonephritis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-8039","authenticated-orcid":true,"given":"Lisa K.","family":"McLellan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-7290","authenticated-orcid":true,"given":"Michael 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L.","family":"Daugherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-2000","authenticated-orcid":true,"given":"Teri N.","family":"Hreha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Janetka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-2689","authenticated-orcid":true,"given":"Daved H.","family":"Fremont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-564X","authenticated-orcid":true,"given":"Scott J.","family":"Hultgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-7628","authenticated-orcid":true,"given":"Herbert W.","family":"Virgin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9848-0975","authenticated-orcid":true,"given":"David A.","family":"Hunstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"key":"ppat.1009314.ref001","doi-asserted-by":"crossref","first-page":"e52835","DOI":"10.1371\/journal.pone.0052835","article-title":"Chaperone-usher fimbriae of Escherichia coli.","volume":"8","author":"DJ Wurpel","year":"2013","journal-title":"PLoS One"},{"key":"ppat.1009314.ref002","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3390\/pathogens5010030","article-title":"Adhesive pili in UTI pathogenesis and drug development","volume":"5","author":"CN 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