{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:52:01Z","timestamp":1787028721170,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian agencies National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro"},{"name":"NIH","award":["R01AI173328"],"award-info":[{"award-number":["R01AI173328"]}]},{"name":"Einstein 2030 Seed Fund","award":["R21AI156104"],"award-info":[{"award-number":["R21AI156104"]}]},{"name":"Einstein 2030 Seed Fund","award":["RO1AI171093"],"award-info":[{"award-number":["RO1AI171093"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Candidozyma auris is an emerging multidrug-resistant fungal pathogen associated with severe invasive infections and high mortality, particularly in healthcare environments. Its rapid global expansion and resistance to multiple antifungal classes pose major challenges to treatment and containment. Extracellular vesicles (EVs) have recently been recognized as important mediators of fungal communication, virulence, and stress adaptation. Here, we examine how caspofungin, a frontline echinocandin, reshapes the EV metabolome of C. auris. Caspofungin exposure drives pronounced remodeling of EV size distributions, yielding a predominance of smaller, more uniform EVs alongside a minor population of larger subtypes. Metabolomic profiling of EVs revealed marked enrichment of metabolites involved in nucleotide salvage and recycling, along with altered amino acid abundances, including increases in amino acids associated with stress responses and redox regulation. These changes are consistent with altered nucleotide turnover and amino acid metabolism under antifungal stress. Importantly, these metabolic alterations reflect caspofungin-induced changes in cellular metabolism that are selectively exported via extracellular vesicles, rather than metabolic activity occurring within the vesicles themselves. Export of these metabolites via EVs may support population-level coordination, biofilm remodeling, and modulation of host immune responses, contributing to echinocandin tolerance. Together, our findings highlight nucleotide- and amino acid-associated metabolic features of EVs as informative readouts of caspofungin exposure and highlight the EV metabolome as a promising source of non-invasive biomarkers for monitoring drug exposure and resistance. This work advances understanding of C. auris adaptation under antifungal stress and reveals new opportunities for therapeutic and diagnostic innovation against this high-priority pathogen.<\/jats:p>","DOI":"10.3390\/jof12020156","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T08:58:21Z","timestamp":1771837101000},"page":"156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Caspofungin Reshapes the Extracellular Vesicles Metabolome of Candidozyma (Candida) auris, Altering Amino Acid and Nucleotide Metabolism"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-3183","authenticated-orcid":false,"given":"Vinicius","family":"Alves","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Laborat\u00f3rio de Biof\u00edsica de Fungos, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6156-1798","authenticated-orcid":false,"given":"Claire V.","family":"Mulholland","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zamith-Miranda","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5875-9886","authenticated-orcid":false,"given":"Susana","family":"Frases","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biof\u00edsica de Fungos, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Rede Micologia RJ, Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Berney","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9905-5754","authenticated-orcid":false,"given":"Joshua D.","family":"Nosanchuk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Medicine (Infectious Diseases), Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e01588-17","DOI":"10.1128\/JCM.01588-17","article-title":"Candida auris: An Emerging Fungal Pathogen","volume":"56","author":"Spivak","year":"2018","journal-title":"J. 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