{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:31:35Z","timestamp":1790922695606,"version":"4.1.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T00:00:00Z","timestamp":1353369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2012,12,31]],"date-time":"2012-12-31T00:00:00Z","timestamp":1356912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2012,12,31]]},"abstract":"ABSTRACT<\/jats:title>\n \n Pathogenic bacteria require iron for replication within their host.\n Klebsiella pneumoniae<\/jats:named-content>\n and other Gram-negative pathogens produce the prototypical siderophore enterobactin (Ent) to scavenge iron\n in vivo<\/jats:italic>\n . In response, mucosal surfaces secrete lipocalin 2 (Lcn2), an innate immune protein that binds Ent to disrupt bacterial iron acquisition and promote acute inflammation during colonization. A subset of\n K. pneumoniae<\/jats:named-content>\n isolates attempt to evade Lcn2 by producing glycosylated Ent (Gly-Ent, salmochelin) or the alternative siderophore yersiniabactin (Ybt). However, these siderophores are not functionally equivalent and differ in their abilities to promote growth in the upper respiratory tract, lungs, and serum. To understand how Lcn2 exploits functional differences between siderophores, isogenic mutants of an Ent\n +<\/jats:sup>\n Gly-Ent\n +<\/jats:sup>\n Ybt\n +<\/jats:sup>\n K. pneumoniae<\/jats:named-content>\n strain were inoculated into\n Lcn2<\/jats:italic>\n +\/+<\/jats:sup>\n and\n Lcn2<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice, and the pattern of pneumonia was examined. Lcn2 effectively protected against the\n iroA ybtS<\/jats:italic>\n mutant (Ent\n +<\/jats:sup>\n Gly-Ent\n \u2212<\/jats:sup>\n Ybt\n \u2212<\/jats:sup>\n ).\n Lcn2<\/jats:italic>\n +\/+<\/jats:sup>\n mice had small foci of pneumonia, whereas\n Lcn2<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice had many bacteria in the perivascular space. The\n entB<\/jats:italic>\n mutant (Ent\n \u2212<\/jats:sup>\n Ybt\n +<\/jats:sup>\n Gly-Ent\n \u2212<\/jats:sup>\n ) caused moderate bronchopneumonia but did not invade the transferrin-containing perivascular space. Accordingly, transferrin blocked Ybt-dependent growth\n in vitro<\/jats:italic>\n . The wild type and the\n iroA<\/jats:italic>\n mutant, which both produce Ent and Ybt, had a mixed phenotype, causing a moderate bronchopneumonia in\n Lcn2<\/jats:italic>\n +\/+<\/jats:sup>\n mice and perivascular overgrowth in\n Lcn2<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice. Together, these data indicate that Lcn2, in combination with transferrin, confines\n K. pneumoniae<\/jats:named-content>\n to the airways and prevents invasion into tissue containing the pulmonary vasculature.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n Gram-negative bacteria are a common cause of severe hospital-acquired infections. To cause disease, they must obtain iron and secrete the small molecule enterobactin to do so. Animal models of pneumonia using\n Klebsiella pneumoniae<\/jats:named-content>\n indicate that enterobactin promotes severe disease. Accordingly, the host defense protein lipocalin 2 exploits this common target by binding enterobactin and disrupting its function. However, pathogenic bacteria often make additional siderophores that lipocalin 2 cannot bind, such as yersiniabactin, which could make this host defense ineffective. This work compares the pattern and severity of pneumonia caused by\n K. pneumoniae<\/jats:named-content>\n based on which siderophores it produces. The results indicate that enterobactin promotes growth around blood vessels that are rich in the iron-binding protein transferrin, but yersiniabactin does not. Together, transferrin and lipocalin 2 protect this space against all types of\n K. pneumoniae<\/jats:named-content>\n tested. Therefore, the ability to acquire iron determines where bacteria can grow in the lung.\n <\/jats:p>","DOI":"10.1128\/mbio.00224-11","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T20:20:43Z","timestamp":1353442843000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":159,"title":["Interaction of Lipocalin 2, Transferrin, and Siderophores Determines the Replicative Niche of Klebsiella pneumoniae during Pneumonia"],"prefix":"10.1128","volume":"3","author":[{"given":"Michael A.","family":"Bachman","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Lenio","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Oyler","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey N.","family":"Weiser","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA"},{"name":"Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"E. coli and salmonella","author":"Earhart CF","year":"1996","unstructured":"EarhartCF . 1996. Uptake and metabolism of iron and molybdenum. In NeidhartF , E. coli and salmonella. ASM Press, Washington, DC."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01529.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","unstructured":"SkaarEP\n. 2010. The battle for iron between bacterial pathogens and their vertebrate hosts. 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