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To acquire heme from the host,\n              <jats:italic>H. ducreyi<\/jats:italic>\n              expresses a TonB-dependent hemoglobin receptor, HgbA, which is necessary and sufficient for\n              <jats:italic>H. ducreyi<\/jats:italic>\n              to progress to the pustular stage of disease in a controlled human infection model. HgbA transports hemoglobin across the outer membrane; how heme is transported across the cytoplasmic membrane is unclear. In previous studies, transcripts encoding the YfeABCD heme transporter were upregulated in experimental lesions caused by\n              <jats:italic>H. ducreyi<\/jats:italic>\n              in human volunteers, suggesting the latter may have a role in virulence. Here we constructed a double deletion mutant, 35000HP\u0394\n              <jats:italic>yfeAB<\/jats:italic>\n              \u0394\n              <jats:italic>yfeCD<\/jats:italic>\n              , which exhibited growth defects relative to its parent 35000HP in media containing human hemoglobin as an iron source. Five human volunteers were inoculated at three sites on the skin overlying the deltoid with each strain. The results of the trial showed that papules formed at 100% (95% CI, 71.5, 100) at both 35000HP and 35000HP\u0394\n              <jats:italic>yfeAB<\/jats:italic>\n              \u0394\n              <jats:italic>yfeCD<\/jats:italic>\n              -inoculated sites (\n              <jats:italic>P<\/jats:italic>\n              = 1.0). Pustules formed at 60% (95% CI, 25.9, 94.1) at parent-inoculated sites and 53% (95% CI, 18.3, 88.4) at mutant-inoculated sites (\n              <jats:italic>P<\/jats:italic>\n              = 0.79). Thus, the ABC transporter encoded by\n              <jats:italic>yfeAB<\/jats:italic>\n              and\n              <jats:italic>yfeCD<\/jats:italic>\n              was dispensable for\n              <jats:italic>H. ducreyi<\/jats:italic>\n              virulence in humans. In the absence of YfeABCD,\n              <jats:italic>H. ducreyi<\/jats:italic>\n              likely utilizes other periplasmic binding proteins and ABC-transporters such as HbpA, SapABCDF, and DppBCDF to shuttle heme from the periplasm into the cytoplasm, underscoring the importance of redundancy of such systems in gram-negative pathogens.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00058-24","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T12:34:18Z","timestamp":1716467658000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A\n            <i>Haemophilus ducreyi<\/i>\n            strain lacking the\n            <i>yfeABCD<\/i>\n            iron transport system is virulent in human volunteers"],"prefix":"10.1128","volume":"92","author":[{"given":"Kate R.","family":"Fortney","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5277-3692","authenticated-orcid":true,"given":"Julie A.","family":"Brothwell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa A.","family":"Batteiger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rory","family":"Duplantier","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry P.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-9911","authenticated-orcid":true,"given":"Stanley M.","family":"Spinola","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA"},{"name":"Department of Medicine, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA"},{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","first-page":"689","volume-title":"Sexually transmitted diseases","author":"Spinola SM","year":"2008","unstructured":"SpinolaSM. 2008. 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