{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T21:24:14Z","timestamp":1781126654636,"version":"3.54.1"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Coordinaci\u00f3n de la Investigaci\u00f3n Cient\u00edfica de la Universidad Michoacana de San Nicol\u00e1s de Hidalgo (CIC\/UMSNH)","award":["2.36"],"award-info":[{"award-number":["2.36"]}]},{"name":"the Coordinaci\u00f3n de la Investigaci\u00f3n Cient\u00edfica de la Universidad Michoacana de San Nicol\u00e1s de Hidalgo (CIC\/UMSNH)","award":["2.26"],"award-info":[{"award-number":["2.26"]}]},{"name":"the Coordinaci\u00f3n de la Investigaci\u00f3n Cient\u00edfica de la Universidad Michoacana de San Nicol\u00e1s de Hidalgo (CIC\/UMSNH)","award":["CONACYT INFRA-2015-01-252013"],"award-info":[{"award-number":["CONACYT INFRA-2015-01-252013"]}]},{"name":"the Coordinaci\u00f3n de la Investigaci\u00f3n Cient\u00edfica de la Universidad Michoacana de San Nicol\u00e1s de Hidalgo (CIC\/UMSNH)","award":["317105"],"award-info":[{"award-number":["317105"]}]},{"name":"CONAHCYT","award":["2.36"],"award-info":[{"award-number":["2.36"]}]},{"name":"CONAHCYT","award":["2.26"],"award-info":[{"award-number":["2.26"]}]},{"name":"CONAHCYT","award":["CONACYT INFRA-2015-01-252013"],"award-info":[{"award-number":["CONACYT INFRA-2015-01-252013"]}]},{"name":"CONAHCYT","award":["317105"],"award-info":[{"award-number":["317105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>This study analyzed the role of blood serum in enhancing the mitochondrial metabolism and virulence of Mucorales through rhizoferrin secretion. We observed that the spores of clinically relevant Mucorales produced in the presence of serum exhibited higher virulence in a heterologous infection model of Galleria mellonella. Cell-free supernatants of the culture broth obtained from spores produced in serum showed increased toxicity against Caenorhabditis elegans, which was linked with the enhanced secretion of rhizoferrin. Spores from Mucoralean species produced or germinated in serum showed increased respiration rates and reactive oxygen species levels. The addition of non-lethal concentrations of potassium cyanide and N-acetylcysteine during the aerobic or anaerobic growth of Mucorales decreased the toxicity of the cell-free supernatants of the culture broth, suggesting that mitochondrial metabolism is important for serum-induced virulence. In support of this hypothesis, a mutant strain of Mucor lusitanicus that lacks fermentation and solely relies on oxidative metabolism exhibited virulence levels comparable to those of the wild-type strain under serum-induced conditions. Contrary to the lower virulence observed, even in the serum, the ADP-ribosylation factor-like 2 deletion strain exhibited decreased mitochondrial activity. Moreover, spores produced in the serum of M. lusitanicus and Rhizopus arrhizus that grew in the presence of a mitophagy inducer showed low virulence. These results suggest that serum-induced mitochondrial activity increases rhizoferrin levels, making Mucorales more virulent.<\/jats:p>","DOI":"10.3390\/jof9121127","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T08:47:43Z","timestamp":1700642863000},"page":"1127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Blood Serum Stimulates the Virulence Potential of Mucorales through Enhancement in Mitochondrial Oxidative Metabolism and Rhizoferrin Production"],"prefix":"10.3390","volume":"9","author":[{"given":"Jos\u00e9 Alberto","family":"Pati\u00f1o-Medina","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Qu\u00edmico Biol\u00f3gicas, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viridiana","family":"Alejandre-Casta\u00f1eda","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Qu\u00edmico Biol\u00f3gicas, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Iv\u00e1n","family":"Valle-Maldonado","sequence":"additional","affiliation":[{"name":"Laboratorio Estatal de Salud P\u00fablica del Estado de Michoac\u00e1n, Morelia 58279, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro Manuel","family":"Mart\u00ednez-Pacheco","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Qu\u00edmico Biol\u00f3gicas, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le\u00f3n Francisco","family":"Ruiz-Herrera","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Qu\u00edmico Biol\u00f3gicas, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-9120","authenticated-orcid":false,"given":"Joel","family":"Ram\u00edrez-Emiliano","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas, Universidad de Guanajuato, Le\u00f3n 37320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4354-5468","authenticated-orcid":false,"given":"Oscar Abelardo","family":"Ram\u00edrez-Marroqu\u00edn","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica Aplicada, Universidad Papaloapan, Campus Tuxtepec, Tuxtepec 68301, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4292-1356","authenticated-orcid":false,"given":"Karla Viridiana","family":"Castro-Cerritos","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica Aplicada, Universidad Papaloapan, Campus Tuxtepec, Tuxtepec 68301, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Campos-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Qu\u00edmico Biol\u00f3gicas, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha Isela","family":"Ram\u00edrez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Qu\u00edmico Biol\u00f3gicas, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-1726","authenticated-orcid":false,"given":"Victoriano","family":"Garre","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica y Microbiolog\u00eda, Universidad de Murcia, 30100 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2160-2903","authenticated-orcid":false,"given":"Ulrike","family":"Binder","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Meza-Carmen","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Qu\u00edmico Biol\u00f3gicas, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lax, C., P\u00e9rez-Arques, C., Navarro-Mendoza, M.I., C\u00e1novas-M\u00e1rquez, J.T., Tahiri, G., P\u00e9rez-Ruiz, J.A., Osorio-Concepci\u00f3n, M., Murcia-Flores, L., Navarro, E., and Garre, V. 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