{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T07:23:49Z","timestamp":1769585029508,"version":"3.49.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["RM1181641E9150B3"],"award-info":[{"award-number":["RM1181641E9150B3"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host\u2019s immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> with that of laboratory-induced resistant strains by challenging <jats:italic>G<\/jats:italic>. <jats:italic>mellonella<\/jats:italic> larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host\u2019s environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> invasiveness and lethality.<\/jats:p>","DOI":"10.1371\/journal.pone.0252555","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T18:49:50Z","timestamp":1622573390000},"page":"e0252555","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence"],"prefix":"10.1371","volume":"16","author":[{"given":"Bruno","family":"Maras","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Maggiore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Mignogna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"D\u2019Erme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0473-5587","authenticated-orcid":true,"given":"Letizia","family":"Angiolella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"issue":"165","key":"pone.0252555.ref001","doi-asserted-by":"crossref","first-page":"165rv13","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: human fungal infections","volume":"4","author":"GD Brown","year":"2012","journal-title":"Sci Transl Med"},{"key":"pone.0252555.ref002","doi-asserted-by":"crossref","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis","volume":"4","author":"PG Pappas","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"pone.0252555.ref003","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3390\/jof6010016","article-title":"On Commensalism of Candida","volume":"6","author":"JA Romo","year":"2020","journal-title":"J Fungi (Basel)."},{"key":"pone.0252555.ref004","first-page":"fuaa060","article-title":"The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives","author":"C d\u2019Enfert","year":"2020","journal-title":"FEMS Microbiol Rev"},{"key":"pone.0252555.ref005","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.3389\/fmicb.2019.02993","article-title":"The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species","volume":"10","author":"R Garcia-Rubio","year":"2020","journal-title":"Front Microbiol."},{"issue":"3","key":"pone.0252555.ref006","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1556\/amicr.54.2007.3.1","article-title":"Pathogenicity and drug resistance in Candida albicans and other yeast species","volume":"54","author":"NN Mishra","year":"2007","journal-title":"A review. 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