{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:58:46Z","timestamp":1787500726902,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian Agencies: Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa no Estado do Rio de Janeiro (FAPERJ)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for approximately 6.8 million deaths worldwide, threatening more than 753 million individuals. People with severe coronavirus disease-2019 (COVID-19) infection often exhibit an immunosuppression condition, resulting in greater chances of developing co-infections with bacteria and fungi, including opportunistic yeasts belonging to the Saccharomyces and Candida genera. In the present work, we have reported the case of a 75-year-old woman admitted at a Brazilian university hospital with an arterial ulcer in the left foot, which was being prepared for surgical amputation. The patient presented other underlying diseases and presented positive tests for COVID-19 prior to hospitalization. She received antimicrobial treatment, but her general condition worsened quickly, leading to death by septic shock after 4 days of hospitalization. Blood samples collected on the day she died were positive for yeast-like organisms, which were later identified as Saccharomyces cerevisiae by both biochemical and molecular methods. The fungal strain exhibited low minimal inhibitory concentration values for the antifungal agents tested (amphotericin B, 5-flucytosine, caspofungin, fluconazole and voriconazole), and it was able to produce important virulence factors, such as extracellular bioactive molecules (e.g., aspartic peptidase, phospholipase, esterase, phytase, catalase, hemolysin and siderophore) and biofilm. Despite the activity against planktonic cells, the antifungals were not able to impact the mature biofilm parameters (biomass and viability). Additionally, the S. cerevisiae strain caused the death of Tenebrio molitor larvae, depending on the fungal inoculum, and larvae immunosuppression with corticosteroids increased the larvae mortality rate. In conclusion, the present study highlighted the emergence of S. cerevisiae as an opportunistic fungal pathogen in immunosuppressed patients presenting several severe comorbidities, including COVID-19 infection.<\/jats:p>","DOI":"10.3390\/tropicalmed8020099","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T05:44:45Z","timestamp":1675316685000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["SARS-CoV-2 Post-Infection and Sepsis by Saccharomyces cerevisiae: A Fatal Case Report\u2014Focus on Fungal Susceptibility and Potential Virulence Attributes"],"prefix":"10.3390","volume":"8","author":[{"given":"L\u00edvia","family":"Ramos","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), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mokus","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), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3132-0878","authenticated-orcid":false,"given":"Heloisa","family":"Frota","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), Universidade Federal do Rio de Janeiro (UFRJ), 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, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","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), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","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), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoel","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz (IOC), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto Oswaldo Cruz (IOC), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4207-3473","authenticated-orcid":false,"given":"Ana","family":"Alves","sequence":"additional","affiliation":[{"name":"Unidade Docente-Assistencial de Dermatologia, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20551-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a","family":"Bernardes-Engemann","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia, Hospital Universit\u00e1rio Pedro Ernesto (HUPE), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20551-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosane","family":"Orofino-Costa","sequence":"additional","affiliation":[{"name":"Unidade Docente-Assistencial de Dermatologia, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20551-030, Brazil"},{"name":"Laborat\u00f3rio de Micologia, Hospital Universit\u00e1rio Pedro Ernesto (HUPE), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20551-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Aor","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), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil"},{"name":"Laborat\u00f3rio de Micologia, Hospital Universit\u00e1rio Pedro Ernesto (HUPE), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20551-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-8148","authenticated-orcid":false,"given":"Marta","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), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil"},{"name":"Rede Micologia RJ\u2014Funda\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","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), Universidade Federal do Rio de Janeiro (UFRJ), 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, Brazil"},{"name":"Rede Micologia RJ\u2014Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41479-021-00083-w","article-title":"The role of co-infections and secondary infections in patients with COVID-19","volume":"13","author":"Feldman","year":"2021","journal-title":"Pneumonia"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Musuuza, J.S., Watson, L., Parmasad, V., Putman-Buehler, N., Christensen, L., and Safdar, N. (2021). Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251170"},{"key":"ref_3","first-page":"1522","article-title":"Opportunistic strains of Saccharomyces cerevisiae: A potential risk sold in food products","volume":"6","author":"Querol","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.mmcr.2017.02.002","article-title":"Catheter-related Saccharomyces cerevisiae fungemia following Saccharomyces boulardii probiotic treatment: In a child in intensive care unit and review of the literature","volume":"15","author":"Soysal","year":"2017","journal-title":"Med. Mycol. Case Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ventoulis, I., Sarmourli, T., Amoiridou, P., Mantzana, P., Exindari, M., Gioula, G., and Vyzantiadis, T.A. (2020). Bloodstream infection by Saccharomyces cerevisiae in two COVID-19 patients after receiving supplementation of Saccharomyces in the ICU. J. Fungi, 6.","DOI":"10.3390\/jof6030098"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"000250","DOI":"10.1099\/acmi.0.000250","article-title":"Bloodstream infection by Saccharomyces cerevisiae in a COVID-19 patient receiving probiotic supplementation in the ICU in Brazil","volume":"3","author":"Pinto","year":"2021","journal-title":"Access Microbiol."},{"key":"ref_7","unstructured":"CLSI (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, CLSI. [3rd ed.]. Approved Standard, CLSI Document M27A3."},{"key":"ref_8","unstructured":"CLSI (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, CLSI. Third Informational Supplement, CLSI Document M27-S3."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/00362178285380341","article-title":"A comparison of secretory proteinases from different strains of Candida albicans","volume":"20","author":"Ruchel","year":"1982","journal-title":"Sabouraudia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.ijmm.2015.08.003","article-title":"Candida parapsilosis (sensu lato) isolated from hospitals located in the Southeast of Brazil: Species distribution, antifungal susceptibility and virulence attributes","volume":"305","author":"Ziccardi","year":"2015","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1080\/00362178285380031","article-title":"Plate method for detection of phospholipase activity in Candida albicans","volume":"20","author":"Price","year":"1982","journal-title":"Sabouraudia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1177\/147323000203000315","article-title":"Esterase activity in various Candida species","volume":"30","author":"Aktas","year":"2002","journal-title":"J. Int. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s11046-011-9453-3","article-title":"Differential phytate utilization in Candida species","volume":"172","author":"Tsang","year":"2011","journal-title":"Mycopathologia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1128\/JCM.39.8.2971-2974.2001","article-title":"Candida species exhibit differential in vitro hemolytic activities","volume":"39","author":"Luo","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s00425-015-2340-2","article-title":"A natural rice rhizospheric bacterium abates arsenic accumulation in rice (Oryza sativa L.)","volume":"242","author":"Lakshmanan","year":"2015","journal-title":"Planta"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ramos, L.S., Figueiredo-Carvalho, M.H.G., Silva, L.N., Siqueira, N.L.M., Lima, J.C., Oliveira, S.S., Almeida-Paes, R., Zancop\u00e9-Oliveira, R.M., Azevedo, F.S., and Ferreira, A.L.P. (2022). The threat called Candida haemulonii species complex in Rio de Janeiro State, Brazil: Focus on antifungal resistance and virulence attributes. J. Fungi, 8.","DOI":"10.3390\/jof8060574"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_18","first-page":"e50166","article-title":"Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs","volume":"73","author":"Evans","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.funbio.2020.04.001","article-title":"Secreted aspartyl peptidases by the emerging, opportunistic and multidrug-resistant fungal pathogens comprising the Candida haemulonii complex","volume":"124","author":"Ramos","year":"2020","journal-title":"Fungal Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s12223-018-0651-y","article-title":"Identification of cell-associated and secreted serine-type peptidases in multidrug-resistant emergent pathogens belonging to the Candida haemulonii complex","volume":"64","author":"Souto","year":"2019","journal-title":"Folia Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.mimet.2007.11.010","article-title":"Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates","volume":"72","author":"Peeters","year":"2008","journal-title":"J. Microbiol. Methods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"239519","DOI":"10.1155\/2015\/239519","article-title":"Artemisia princeps inhibits biofilm formation and virulence-factor expression of antibiotic-resistant bacteria","volume":"2015","author":"Choi","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1093\/mmy\/myx005","article-title":"Planktonic growth and biofilm formation profiles in Candida haemulonii species complex","volume":"55","author":"Ramos","year":"2017","journal-title":"Med. Mycol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.mimet.2015.10.004","article-title":"Tenebrio molitor (Coleoptera: Tenebrionidae) as an alternative host to study fungal infections","volume":"118","author":"Morey","year":"2015","journal-title":"J. Microbiol. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00430-016-0450-5","article-title":"Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae","volume":"205","author":"Torres","year":"2016","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.riam.2018.04.004","article-title":"Antifungal susceptibility of Saccharomyces cerevisiae and therapy in a murine model of disseminated infection","volume":"36","author":"Thomson","year":"2019","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ijantimicag.2014.06.007","article-title":"Activity of echinocandins and triazoles against a contemporary (2012) worldwide collection of yeast and moulds collected from invasive infections","volume":"44","author":"Castanheira","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s11046-011-9414-x","article-title":"Saccharomyces cerevisiae vaginitis: Microbiology and in vitro antifungal susceptibility","volume":"172","author":"Eraso","year":"2011","journal-title":"Mycopathologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1128\/JCM.01747-08","article-title":"Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing","volume":"47","author":"Pfaller","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10482-006-9077-7","article-title":"A comparison of clinical and food Saccharomyces cerevisiae isolates on the basis of potential virulence factors","volume":"90","author":"Querol","year":"2006","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Imre, A., Kov\u00e1cs, R., P\u00e1zm\u00e1ndi, K., Nemes, D., Jakab, \u00c1., Fekete, T., R\u00e1cz, H.V., D\u00f3czi, I., B\u00e1cskay, I., and G\u00e1cser, A. (2021). Virulence factors and in-host selection on phenotypes in infectious probiotic yeast isolates (Saccharomyces \u2018boulardii\u2019). J. Fungi, 7.","DOI":"10.3390\/jof7090746"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"796394","DOI":"10.4061\/2011\/796394","article-title":"Improvement of phytase activity by a new Saccharomyces cerevisiae strain using statistical optimization","volume":"2011","author":"Ries","year":"2011","journal-title":"Enzym. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"179","DOI":"10.4265\/bio.21.179","article-title":"Roles of catalase and trehalose in the protection from hydrogen peroxide toxicity in Saccharomyces cerevisiae","volume":"21","author":"Nishimoto","year":"2016","journal-title":"Biocontrol Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"659328","DOI":"10.3389\/fnut.2021.659328","article-title":"Safety evaluation of yeasts with probiotic potential","volume":"8","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bojsen, R., Regenberg, B., and Folkesson, A. (2014). Saccharomyces cerevisiae biofilm tolerance towards systemic antifungals depends on growth phase. BMC Microbiol., 14.","DOI":"10.1186\/s12866-014-0305-4"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Canteri de Souza, P., Cust\u00f3dio Caloni, C., Wilson, D., and Sergio Almeida, R. (2018). An invertebrate host to study fungal infections, mycotoxins and antifungal drugs: Tenebrio molitor. J. Fungi, 4.","DOI":"10.3390\/jof4040125"}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/8\/2\/99\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:22:14Z","timestamp":1760120534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/8\/2\/99"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["tropicalmed8020099"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed8020099","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]}}}