{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:57:43Z","timestamp":1792461463386,"version":"4.5.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"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":"crossref","award":["R01AI141360"],"award-info":[{"award-number":["R01AI141360"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U19 AI110820"],"award-info":[{"award-number":["U19 AI110820"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,1,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Mucormycosis is classified by the National Institute of Allergy and Infectious Diseases as an emerging disease and is caused by\n            <jats:italic>Mucorales<\/jats:italic>\n            fungi. Despite the high morbidity and mortality rates associated with the disease, little is known about the host-pathogen interactions that dictate disease progression. The recent surge of mucormycosis cases among COVID-19 patients has thrust the disease and the lack of available treatments into the spotlight. Despite severe fungal angioinvasion and tissue necrosis during infection, clinical observations suggest a lack of pro-inflammatory responses. Understanding immune evasion mechanisms in mucormycosis can help guide potential therapeutic options. In this study, we demonstrate that\n            <jats:italic>Mucorales<\/jats:italic>\n            fungi can suppress the accumulation of nitric oxide (NO) in lipopolysaccharide- and interferon gamma-stimulated macrophages despite robust expression of the\n            <jats:italic>Nos2<\/jats:italic>\n            mRNA and inducible nitric oxide synthase protein. This suppressive activity requires fungal viability and direct contact with macrophages and is not due to restricted access to L-arginine substrate. While\n            <jats:italic>Mucorales<\/jats:italic>\n            fungi appear to be able to remove NO from its environment, it does not account for the full suppression that we observe and suggests that\n            <jats:italic>Mucorales<\/jats:italic>\n            employs at least two mechanisms. Future experiments will elucidate the mechanisms by which\n            <jats:italic>Mucorales<\/jats:italic>\n            fungi deplete NO accumulation by macrophages and the implications of this depletion in mucormycosis pathogenesis.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              In October 2022,\n              <jats:italic>Mucorales<\/jats:italic>\n              fungi were listed in the \u201cHigh Priority Group\u201d on the first-ever list of fungal priority pathogens by the World Health Organization. As the causative agent of mucormycosis,\n              <jats:italic>Mucorales<\/jats:italic>\n              have become of great clinical and public health importance with growing mucormycosis numbers, notably with the exponential rise of COVID-19-associated mucormycosis cases. Despite the dire need, there are limited therapeutic options to treat mucormycosis. Our research fills in critical gaps of knowledge about how\n              <jats:italic>Mucorales<\/jats:italic>\n              fungi evade the host immune system. Specifically, we offer evidence that\n              <jats:italic>Mucorales<\/jats:italic>\n              block nitric oxide production, which is a key mediator and signaling molecule of the mammalian innate immune response to microbial pathogens. Our work offers new insight into immune evasion mechanisms by\n              <jats:italic>Mucorales<\/jats:italic>\n              fungi.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02848-23","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T14:03:50Z","timestamp":1702562630000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["<i>Mucorales<\/i>\n            fungi suppress nitric oxide production by macrophages"],"prefix":"10.1128","volume":"15","author":[{"given":"Alexandra Y.","family":"Soare","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-2015","authenticated-orcid":true,"given":"Vincent M.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/432579"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07301-y"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00826-w"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.01.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.06.010"},{"key":"e_1_3_3_7_2","doi-asserted-by":"crossref","unstructured":"Bath PM Coleman CM Gordon AL Lim WS Webb AJ. 2021. Nitric oxide for the prevention and treatment of viral bacterial protozoal and fungal infections version 2. Peer review: 1 approved. F1000Research 10","DOI":"10.12688\/f1000research.51270.2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01820-16"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-765X.2008.02373.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43718"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof6020085"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-016-0879-x"},{"key":"e_1_3_3_13_2","first-page":"888","article-title":"A phase 2, controlled, dose-ranging study of SB208, an investigational topical nitric oxide-releasing drug, for the treatment of tinea pedis","volume":"17","author":"Elewski BE","year":"2018","unstructured":"Elewski BE, Kircik LH, Stasko N, De Leon E, Enloe C, Durham T, Maeda-Chubachi T. 2018. A phase 2, controlled, dose-ranging study of SB208, an investigational topical nitric oxide-releasing drug, for the treatment of tinea pedis. J Drugs Dermatol 17:888\u2013893.","journal-title":"J Drugs Dermatol"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00578-07"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2015.03.012"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00469"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2017.54"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01249-10"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac492.1724"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abd.2020.03.004"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmr.2022.10.002"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mmcr.2019.12.005"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096203"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2010.11.006"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1997.1166"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01249-10"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14465"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10110429"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14433-7"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.02848-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.02848-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T15:43:23Z","timestamp":1705419803000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.02848-23"}},"subtitle":[],"editor":[{"given":"Michael","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,16]]}},"alternative-id":["10.1128\/mbio.02848-23"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02848-23","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,16]]},"assertion":[{"value":"2023-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02848-23"}}