{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T19:36:51Z","timestamp":1780774611569,"version":"3.54.1"},"reference-count":85,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"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":["Infect Immun"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Nontypeable\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Haemophilus influenzae<\/jats:named-content>\n            (NTHI) is a commensal inhabitant of the human nasopharynx and a causative agent of otitis media and other diseases of the upper and lower human airway. During colonization within the host, NTHI must acquire essential nutrients and evade immune attack. We previously demonstrated that the NTHI Sap transporter, an inner membrane protein complex, mediates resistance to antimicrobial peptides and is required for heme homeostasis. We hypothesized that Sap transporter functions are critical for NTHI interaction with the host epithelium and establishment of colonization. Thus, we cocultured the parent or the\n            <jats:italic>sapA<\/jats:italic>\n            mutant on polarized epithelial cells grown at an air-liquid interface, as a physiological model of NTHI colonization, to determine the contribution of the Sap transporter to bacterium-host cell interactions. Although SapA-deficient NTHI was less adherent to epithelial cells, we observed a significant increase in invasive bacteria compared to the parent strain. Upon internalization, the\n            <jats:italic>sapA<\/jats:italic>\n            mutant appeared free in the cytoplasm, whereas the parent strain was primarily found in endosomes, indicating differential subcellular trafficking. Additionally, we observed reduced inflammatory cytokine production by the epithelium in response to the\n            <jats:italic>sapA<\/jats:italic>\n            mutant strain compared to the parental strain. Furthermore, chinchilla middle ears challenged with the\n            <jats:italic>sapA<\/jats:italic>\n            mutant demonstrated a decrease in disease severity compared to ears challenged with the parental strain. Collectively, our data suggest that NTHI senses host environmental cues via Sap transporter function to mediate interaction with host epithelial cells. Epithelial cell invasion and modulation of host inflammatory cytokine responses may promote NTHI colonization and access to essential nutrients.\n          <\/jats:p>","DOI":"10.1128\/iai.00942-12","type":"journal-article","created":{"date-parts":[[2012,10,16]],"date-time":"2012-10-16T01:48:39Z","timestamp":1350352119000},"page":"43-54","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["The Haemophilus influenzae Sap Transporter Mediates Bacterium-Epithelial Cell Homeostasis"],"prefix":"10.1128","volume":"81","author":[{"given":"Forrest K.","family":"Raffel","sequence":"first","affiliation":[{"name":"The Research Institute at Nationwide Children's Hospital and The Ohio State University College of Medicine, Department of Pediatrics, Center for Microbial Pathogenesis, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake R.","family":"Szelestey","sequence":"additional","affiliation":[{"name":"The Research Institute at Nationwide Children's Hospital and The Ohio State University College of Medicine, Department of Pediatrics, Center for Microbial Pathogenesis, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wandy L.","family":"Beatty","sequence":"additional","affiliation":[{"name":"The Research Institute at Nationwide Children's Hospital and The Ohio State University College of Medicine, Department of Pediatrics, Center for Microbial Pathogenesis, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Mason","sequence":"additional","affiliation":[{"name":"The Research Institute at Nationwide Children's Hospital and The Ohio State University College of Medicine, Department of Pediatrics, Center for Microbial Pathogenesis, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/161.3.512"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199702001-00002"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200304000-00009"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200403-354OC"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.4.1450-1459.2004"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.2.336-363.2001"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00277-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00098803"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152449"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2000.917304.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1142"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2836"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1206"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2008.07.002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1975.03240130021018"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.2001.0456"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00320-09"},{"key":"e_1_3_3_19_2","first-page":"1","article-title":"The pathogenesis of disease due to nontypeable Haemophilus influenzae","volume":"71","author":"Hardy GG","year":"2003","unstructured":"HardyGGTudorSMSt GemeJWIII. 2003. 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