{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T07:39:30Z","timestamp":1758267570278,"version":"3.37.3"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013173","name":"Gyeonggi-do Regional Research Center","doi-asserted-by":"publisher","award":["GRRC-KyungHee2020(B04)"],"award-info":[{"award-number":["GRRC-KyungHee2020(B04)"]}],"id":[{"id":"10.13039\/501100013173","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>Candida<\/jats:italic>is an opportunistic pathogen and a common cause of fungal infections worldwide. Anti-fungal use against<jats:italic>Candida<\/jats:italic>infections has resulted in the appearance of resistant strains. The limited choice of anti-fungal therapy means alternative strategies are needed to control fungal infectious diseases. The aim of this study was to evaluate the inhibition of<jats:italic>Candida<\/jats:italic>biofilm formation by<jats:italic>Hedera rhombea<\/jats:italic>(Korean name: songak) extract. Biofilm formation was assessed using the crystal violet assay which showed a dose dependent reduction in the presence of extract with the biofilm formation inhibitory concentration of<jats:italic>C<\/jats:italic>.<jats:italic>albicans<\/jats:italic>(IC<jats:sub>50<\/jats:sub>= 12.5\u03bcg\/ml<jats:italic>)<\/jats:italic>,<jats:italic>C<\/jats:italic>.<jats:italic>tropicalis var<\/jats:italic>.<jats:italic>tropicalis<\/jats:italic>(IC<jats:sub>50<\/jats:sub>= 25\u03bcg\/ml),<jats:italic>C<\/jats:italic>.<jats:italic>parapsilosis var<\/jats:italic>.<jats:italic>parapsilosis<\/jats:italic>(IC<jats:sub>50<\/jats:sub>= 6.25\u03bcg\/ml),<jats:italic>C<\/jats:italic>.<jats:italic>glabrata<\/jats:italic>(IC<jats:sub>50<\/jats:sub>= 6.25\u03bcg\/ml),<jats:italic>C<\/jats:italic>.<jats:italic>tropicalis<\/jats:italic>(IC<jats:sub>50<\/jats:sub>= 12.5\u03bcg\/ml), and<jats:italic>C<\/jats:italic>.<jats:italic>parapsilosis<\/jats:italic>(IC<jats:sub>50<\/jats:sub>= 12.5\u03bcg\/ml) without directly reducing<jats:italic>Candida<\/jats:italic>growth. Treatment with 6.25\u03bcg\/mL of extract increased the antifungal susceptibility to miconazole from 32% decreasing of fungal growth to 98.8% of that based on the fungal growth assay. Treatment of extract dose-dependently reduced the dimorphic transition of<jats:italic>Candida<\/jats:italic>based on the dimorphic transition assay and treatment of 3.125\u03bcg\/mL of extract completely blocked the adherence of<jats:italic>Candida<\/jats:italic>to the HaCaT cells. To know the molecular mechanisms of biofilm formation inhibition by extract, qRT-PCR analysis was done, and the extract was found to dose dependently reduce the expression of hyphal-associated genes (<jats:italic>ALS3<\/jats:italic>,<jats:italic>ECE1<\/jats:italic>,<jats:italic>HWP1<\/jats:italic>,<jats:italic>PGA50<\/jats:italic>, and<jats:italic>PBR1<\/jats:italic>), extracellular matrix genes (<jats:italic>GSC1<\/jats:italic>,<jats:italic>ZAP1<\/jats:italic>,<jats:italic>ADH5<\/jats:italic>, and<jats:italic>CSH1<\/jats:italic>), Ras1-cAMP-PKA pathway genes (<jats:italic>CYR1<\/jats:italic>,<jats:italic>EFG1<\/jats:italic>, and<jats:italic>RAS1<\/jats:italic>), Cph2-Tec1 pathway gene (<jats:italic>TEC1<\/jats:italic>) and MAP kinases pathway gene (<jats:italic>HST7<\/jats:italic>). In this study,<jats:italic>Hedera rhombea<\/jats:italic>extract showed inhibition of fungal biofilm formation, activation of antifungal susceptibility, and reduction of infection. These results suggest that fungal biofilm formation is good screen for developing the antifungal adjuvant and<jats:italic>Hedera rhombea<\/jats:italic>extract should be a good candidate against biofilm-related fungal infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0258108","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T11:51:00Z","timestamp":1633607460000},"page":"e0258108","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hedera rhombea inhibits the biofilm formation of Candida, thereby increases the susceptibility to antifungal agent, and reduces infection"],"prefix":"10.1371","volume":"16","author":[{"given":"Daseul","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0407-3018","authenticated-orcid":true,"given":"Ki-young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"issue":"1","key":"pone.0258108.ref001","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1128\/CMR.00029-06","article-title":"Epidemiology of invasive candidiasis: a persistent public health problem","volume":"20","author":"MA Pfaller","year":"2007","journal-title":"Clin Microbiol Rev"},{"key":"pone.0258108.ref002","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fmed.2018.00028","article-title":"Candida biofilms: threats, challenges, and promising strategies","volume":"5","author":"M 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