{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:51:49Z","timestamp":1790077909457,"version":"4.0.1"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,8,14]],"date-time":"2018-08-14T00:00:00Z","timestamp":1534204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T00:00:00Z","timestamp":1536105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI110820"],"award-info":[{"award-number":["U19AI110820"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI063503"],"award-info":[{"award-number":["AI063503"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI124566"],"award-info":[{"award-number":["R01AI124566"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE022600"],"award-info":[{"award-number":["R01DE022600"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["K99DE026856"],"award-info":[{"award-number":["K99DE026856"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,9,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Mucormycosis is a life-threatening, invasive fungal infection that is caused by various species belonging to the order Mucorales.\n            <jats:italic>Rhizopus<\/jats:italic>\n            species are the most common cause of the disease, responsible for approximately 70% of all cases of mucormycosis. During pulmonary mucormycosis, inhaled\n            <jats:italic>Rhizopus<\/jats:italic>\n            spores must adhere to and invade airway epithelial cells in order to establish infection. The molecular mechanisms that govern this interaction are poorly understood. We performed an unbiased survey of the host transcriptional response during early stages of\n            <jats:named-content content-type=\"genus-species\">Rhizopus arrhizus<\/jats:named-content>\n            var.\n            <jats:named-content content-type=\"genus-species\">delemar<\/jats:named-content>\n            (\n            <jats:named-content content-type=\"genus-species\">R.\u00a0delemar<\/jats:named-content>\n            ) infection in a murine model of pulmonary mucormycosis using transcriptome sequencing (RNA-seq). Network analysis revealed activation of the host\u2019s epidermal growth factor receptor (EGFR) signaling. Consistent with the RNA-seq results, EGFR became phosphorylated upon\n            <jats:italic>in vitro<\/jats:italic>\n            infection of human alveolar epithelial cells with several members of the Mucorales, and this phosphorylated, activated form of EGFR colocalized with\n            <jats:named-content content-type=\"genus-species\">R.\u00a0delemar<\/jats:named-content>\n            spores. Inhibition of EGFR signaling with cetuximab or gefitinib, specific FDA-approved inhibitors of EGFR, significantly reduced the ability of\n            <jats:named-content content-type=\"genus-species\">R.\u00a0delemar<\/jats:named-content>\n            to invade and damage airway epithelial cells. Furthermore, gefitinib treatment significantly prolonged survival of mice with pulmonary mucormycosis, reduced tissue fungal burden, and attenuated the activation of EGFR in response to pulmonary mucormycosis. These results indicate EGFR represents a novel host target to block invasion of alveolar epithelial cells by\n            <jats:named-content content-type=\"genus-species\">R.\u00a0delemar<\/jats:named-content>\n            , and inhibition of EGFR signaling provides a novel approach for treating mucormycosis by repurposing an FDA-approved drug.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Mucormycosis is an increasingly common, highly lethal fungal infection with very limited treatment options. Using a combination of\n            <jats:italic>in vivo<\/jats:italic>\n            animal models, transcriptomics, cell biology, and pharmacological approaches, we have demonstrated that Mucorales fungi activate EGFR signaling to induce fungal uptake into airway epithelial cells. Inhibition of EGFR signaling with existing FDA-approved drugs significantly increased survival following\n            <jats:named-content content-type=\"genus-species\">R.\u00a0arrhizus<\/jats:named-content>\n            var.\n            <jats:named-content content-type=\"genus-species\">delemar<\/jats:named-content>\n            infection in mice. This study enhances our understanding of how Mucorales fungi invade host cells during the establishment of pulmonary mucormycosis and provides a proof-of-concept for the repurposing of FDA-approved drugs that target EGFR function.\n          <\/jats:p>","DOI":"10.1128\/mbio.01384-18","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T07:14:41Z","timestamp":1534144481000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["Inhibition of EGFR Signaling Protects from Mucormycosis"],"prefix":"10.1128","volume":"9","author":[{"given":"Tonya N.","family":"Watkins","sequence":"first","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teclegiorgis","family":"Gebremariam","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Swidergall","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol C.","family":"Shetty","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen T.","family":"Graf","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alqarihi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sondus","family":"Alkhazraji","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar I.","family":"Alsaadi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vonetta L.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott G.","family":"Filler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, USA"},{"name":"David Geffen School of Medicine at UCLA, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf S.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, USA"},{"name":"David Geffen School of Medicine at UCLA, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.2.236-301.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.3.556-569.2005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/432579"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000008"},{"key":"e_1_3_2_6_2","first-page":"524","volume-title":"Medical mycology","author":"Kwon-Chung KJ","year":"1992","unstructured":"Kwon-Chung KJ, Bennett JE. 1992. 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