{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:34:22Z","timestamp":1790742862272,"version":"4.1.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:label\/>\n                  <jats:p>The opportunistic filamentous fungi belonging to the Scedosporium and Lomentospora genera are highly tolerant to all classes of available antifungal drugs. Moreover, the mature biofilm formed by these fungi presents higher antifungal resistance when compared to planktonic cells. Nevertheless, the resistance mechanisms developed by the biofilm lifestyle are not completely elucidated. In the current study, we have investigated the mainly known resistance mechanisms to azoles (voriconazole and fluconazole) and polyenes (amphotericin B [AMB]) in S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans (formerly S. prolificans) biofilms. Both classes of antifungals can physically bind to the extracellular matrix of mature biofilms, preventing the drugs from reaching their targets on biofilm-forming cells, which precludes their activity and toxicity. In addition, the activity of efflux pumps, measured by Rhodamine 6\u00a0G, was increased along with the maturation of the biofilm. The efflux pump's inhibition by L-Phe-L-Arg-\u03b2-naphthylamide culminated in a 2- to 16-fold increase in azole susceptibility in conidial cells, but not in mature biofilms. Finally, we demonstrated by using specific inhibitors that in conidia, but not in biofilms, AMB induced the production of reactive oxygen species through the activity of the oxidative phosphorylation system (complex I\u2013IV and alternative oxidases). However, the cellular redox imbalance caused by AMB was well-coped with the high activity of antioxidative enzymes, such as superoxide dismutase and catalase. Altogether, our results revealed that Scedosporium\/Lomentospora biofilm resistance occurs through various mechanisms that operate concomitantly, which could explain the huge challenge in the clinical treatment of scedosporiosis\/lomentosporiosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Lay Summary<\/jats:title>\n                  <jats:p>Scedosporium\/Lomentospora spp. are multidrug-resistant pathogens able to cause diverse types of infections with typical biofilm characteristics, which makes the treatment a hard issue. We deciphered the resistance mechanisms to classical antifungals developed in the biofilm formed by these fungi.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mmy\/myac036","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T01:16:00Z","timestamp":1654046160000},"source":"Crossref","is-referenced-by-count":19,"title":["Decoding the antifungal resistance mechanisms in biofilms of emerging, ubiquitous and multidrug-resistant species belonging to the <i>Scedosporium\/Lomentospora<\/i> genera"],"prefix":"10.1093","volume":"60","author":[{"given":"Tha\u00eds P","family":"Mello","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Centro de Ci\u00eancias da Sa\u00fade (CCS), Universidade Federal do Rio de Janeiro (UFRJ) , Rio de Janeiro, 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone S C","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Centro de Ci\u00eancias da Sa\u00fade (CCS), Universidade Federal do Rio de Janeiro (UFRJ) , Rio de Janeiro, 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta H","family":"Branquinha","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Centro de Ci\u00eancias da Sa\u00fade (CCS), Universidade Federal do Rio de Janeiro (UFRJ) , Rio de Janeiro, 21941-902, Brazil"},{"name":"Rede Micologia RJ \u2013 Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ) , Rio de Janeiro, 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-8592","authenticated-orcid":false,"given":"Andr\u00e9 L S","family":"Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Centro de Ci\u00eancias da Sa\u00fade (CCS), Universidade Federal do Rio de Janeiro (UFRJ) , Rio de Janeiro, 21941-902, Brazil"},{"name":"Rede Micologia RJ \u2013 Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ) , Rio de Janeiro, 21941-902, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro (UFRJ) , Rio de Janeiro, 21941-909, 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