Evaluation of antifungal spectrum of Cupferron against Candida albicans
Candida albicans is an opportunistic yeast accounting for about 50–90 % of all cases of candidiasis in humans, ranging from superficial to systemic potentially life-threatening infections. The presence of several virulence factors, including biofilm, hyphal transition, and proteolytic enzymes produc...
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creator | Palma, Francesca Acunzo, Marina Della Marca, Roberta Dell’Annunziata, Federica Folliero, Veronica Chianese, Annalisa Zannella, Carla Franci, Gianluigi De Filippis, Anna Galdiero, Massimiliano |
description | Candida albicans is an opportunistic yeast accounting for about 50–90 % of all cases of candidiasis in humans, ranging from superficial to systemic potentially life-threatening infections. The presence of several virulence factors, including biofilm, hyphal transition, and proteolytic enzymes production, worsens the fungal infections burden on healthcare system resources. Hence, developing new bioactive compounds with antifungal activity is a pressing urgence for the scientific community. In this perspective, we evaluated the anti-Candida potential of the N-Nitroso-N-phenylhydroxylamine ammonium salt (cupferron) against standard and clinical C. albicans strains. Firstly, the in vitro cytotoxicity of cupferron was checked in the range 400–12.5 μg/mL against human microglial cells (HMC-3). Secondly, its antifungal spectrum was explored via disk diffusion test, broth-microdilution method, and time-killing curve analysis, validating the obtained results through scanning electron microscopy (SEM) observations. Additionally, we evaluated the cupferron impact on the main virulence determinants of Candida albicans. At non-toxic concentrations (100–12.5 μg/mL), the compound exerted interesting anti-Candida activity, registering a minimum inhibitory concentration (MIC) between 50 and 100 μg/mL against the tested strains, with a fungistatic effect until 100 μg/mL. Furthermore, cupferron was able to counteract fungal virulence at MIC and sub-MIC values (50–12.5 μg/mL). These findings may propose cupferron as a new potential antifungal option for the treatment of Candida albicans infections.
•Antifungal evaluation of cupferron against planktonic and sessile Candida albicans.•Reduction of biofilm, hyphal transition and proteolytic enzymes production.•MIC at 50 μg/mL, with a fungistatic effect until 100 μg/mL.•The cytotoxicity in the range 100–12.5 μg/mL against HMC-3. |
doi_str_mv | 10.1016/j.micpath.2024.106835 |
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•Antifungal evaluation of cupferron against planktonic and sessile Candida albicans.•Reduction of biofilm, hyphal transition and proteolytic enzymes production.•MIC at 50 μg/mL, with a fungistatic effect until 100 μg/mL.•The cytotoxicity in the range 100–12.5 μg/mL against HMC-3.</description><identifier>ISSN: 0882-4010</identifier><identifier>ISSN: 1096-1208</identifier><identifier>EISSN: 1096-1208</identifier><identifier>DOI: 10.1016/j.micpath.2024.106835</identifier><identifier>PMID: 39117014</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>ammonium salts ; Antifungal compound ; antifungal properties ; biofilm ; Candida albicans ; candidiasis ; Cupferron ; cytotoxicity ; disk diffusion antimicrobial test ; Drug-resistance ; electron microscopy ; health services ; humans ; hyphae ; minimum inhibitory concentration ; pathogenesis ; proteolysis ; Virulence ; yeasts</subject><ispartof>Microbial pathogenesis, 2024-09, Vol.194, p.106835, Article 106835</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c276t-7260053203216fc411fda3bd7dda9ea6b7a117ebcc248f537d602c338eb7dcbb3</cites><orcidid>0000-0003-3321-4331 ; 0000-0001-7991-8700 ; 0000-0002-7406-9882 ; 0000-0002-1576-6290 ; 0000-0002-1654-8500 ; 0009-0000-5955-4495 ; 0009-0004-8957-0719</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0882401024003024$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39117014$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Palma, Francesca</creatorcontrib><creatorcontrib>Acunzo, Marina</creatorcontrib><creatorcontrib>Della Marca, Roberta</creatorcontrib><creatorcontrib>Dell’Annunziata, Federica</creatorcontrib><creatorcontrib>Folliero, Veronica</creatorcontrib><creatorcontrib>Chianese, Annalisa</creatorcontrib><creatorcontrib>Zannella, Carla</creatorcontrib><creatorcontrib>Franci, Gianluigi</creatorcontrib><creatorcontrib>De Filippis, Anna</creatorcontrib><creatorcontrib>Galdiero, Massimiliano</creatorcontrib><title>Evaluation of antifungal spectrum of Cupferron against Candida albicans</title><title>Microbial pathogenesis</title><addtitle>Microb Pathog</addtitle><description>Candida albicans is an opportunistic yeast accounting for about 50–90 % of all cases of candidiasis in humans, ranging from superficial to systemic potentially life-threatening infections. The presence of several virulence factors, including biofilm, hyphal transition, and proteolytic enzymes production, worsens the fungal infections burden on healthcare system resources. Hence, developing new bioactive compounds with antifungal activity is a pressing urgence for the scientific community. In this perspective, we evaluated the anti-Candida potential of the N-Nitroso-N-phenylhydroxylamine ammonium salt (cupferron) against standard and clinical C. albicans strains. Firstly, the in vitro cytotoxicity of cupferron was checked in the range 400–12.5 μg/mL against human microglial cells (HMC-3). Secondly, its antifungal spectrum was explored via disk diffusion test, broth-microdilution method, and time-killing curve analysis, validating the obtained results through scanning electron microscopy (SEM) observations. Additionally, we evaluated the cupferron impact on the main virulence determinants of Candida albicans. At non-toxic concentrations (100–12.5 μg/mL), the compound exerted interesting anti-Candida activity, registering a minimum inhibitory concentration (MIC) between 50 and 100 μg/mL against the tested strains, with a fungistatic effect until 100 μg/mL. Furthermore, cupferron was able to counteract fungal virulence at MIC and sub-MIC values (50–12.5 μg/mL). These findings may propose cupferron as a new potential antifungal option for the treatment of Candida albicans infections.
•Antifungal evaluation of cupferron against planktonic and sessile Candida albicans.•Reduction of biofilm, hyphal transition and proteolytic enzymes production.•MIC at 50 μg/mL, with a fungistatic effect until 100 μg/mL.•The cytotoxicity in the range 100–12.5 μg/mL against HMC-3.</description><subject>ammonium salts</subject><subject>Antifungal compound</subject><subject>antifungal properties</subject><subject>biofilm</subject><subject>Candida albicans</subject><subject>candidiasis</subject><subject>Cupferron</subject><subject>cytotoxicity</subject><subject>disk diffusion antimicrobial test</subject><subject>Drug-resistance</subject><subject>electron microscopy</subject><subject>health services</subject><subject>humans</subject><subject>hyphae</subject><subject>minimum inhibitory concentration</subject><subject>pathogenesis</subject><subject>proteolysis</subject><subject>Virulence</subject><subject>yeasts</subject><issn>0882-4010</issn><issn>1096-1208</issn><issn>1096-1208</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkE1LAzEQhoMotlZ_grJHL1snH83unkRKrULBi57DbJKtKftlslvw35vS6tXTwMvzzgwPIbcU5hSofNjNG6d7HD7nDJiImcz54oxMKRQypQzyczKFPGepAAoTchXCDgAKwYtLMuEFpRlQMSXr1R7rEQfXtUlXJdgOrhrbLdZJ6K0e_Ngc4uXYV9b7yOAWXRuGZImtcQYTrEunsQ3X5KLCOtib05yRj-fV-_Il3bytX5dPm1SzTA5pxiTAgjPgjMpKC0org7w0mTFYWJRlhvEzW2rNRF4teGYkMM15bsvM6LLkM3J_3Nv77mu0YVCNC9rWNba2G4PiNJYEzZn4H4Ui-pBUsIgujqj2XQjeVqr3rkH_rSiog261Uyfd6qBbHXXH3t3pxFg21vy1fv1G4PEI2Ohk76xXQTvbamucj3qV6dw_J34AwtmTGQ</recordid><startdate>20240901</startdate><enddate>20240901</enddate><creator>Palma, Francesca</creator><creator>Acunzo, Marina</creator><creator>Della Marca, Roberta</creator><creator>Dell’Annunziata, Federica</creator><creator>Folliero, Veronica</creator><creator>Chianese, Annalisa</creator><creator>Zannella, Carla</creator><creator>Franci, Gianluigi</creator><creator>De Filippis, Anna</creator><creator>Galdiero, Massimiliano</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0003-3321-4331</orcidid><orcidid>https://orcid.org/0000-0001-7991-8700</orcidid><orcidid>https://orcid.org/0000-0002-7406-9882</orcidid><orcidid>https://orcid.org/0000-0002-1576-6290</orcidid><orcidid>https://orcid.org/0000-0002-1654-8500</orcidid><orcidid>https://orcid.org/0009-0000-5955-4495</orcidid><orcidid>https://orcid.org/0009-0004-8957-0719</orcidid></search><sort><creationdate>20240901</creationdate><title>Evaluation of antifungal spectrum of Cupferron against Candida albicans</title><author>Palma, Francesca ; Acunzo, Marina ; Della Marca, Roberta ; Dell’Annunziata, Federica ; Folliero, Veronica ; Chianese, Annalisa ; Zannella, Carla ; Franci, Gianluigi ; De Filippis, Anna ; Galdiero, Massimiliano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c276t-7260053203216fc411fda3bd7dda9ea6b7a117ebcc248f537d602c338eb7dcbb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>ammonium salts</topic><topic>Antifungal compound</topic><topic>antifungal properties</topic><topic>biofilm</topic><topic>Candida albicans</topic><topic>candidiasis</topic><topic>Cupferron</topic><topic>cytotoxicity</topic><topic>disk diffusion antimicrobial test</topic><topic>Drug-resistance</topic><topic>electron microscopy</topic><topic>health services</topic><topic>humans</topic><topic>hyphae</topic><topic>minimum inhibitory concentration</topic><topic>pathogenesis</topic><topic>proteolysis</topic><topic>Virulence</topic><topic>yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Palma, Francesca</creatorcontrib><creatorcontrib>Acunzo, Marina</creatorcontrib><creatorcontrib>Della Marca, Roberta</creatorcontrib><creatorcontrib>Dell’Annunziata, Federica</creatorcontrib><creatorcontrib>Folliero, Veronica</creatorcontrib><creatorcontrib>Chianese, Annalisa</creatorcontrib><creatorcontrib>Zannella, Carla</creatorcontrib><creatorcontrib>Franci, Gianluigi</creatorcontrib><creatorcontrib>De Filippis, Anna</creatorcontrib><creatorcontrib>Galdiero, Massimiliano</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Microbial pathogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Palma, Francesca</au><au>Acunzo, Marina</au><au>Della Marca, Roberta</au><au>Dell’Annunziata, Federica</au><au>Folliero, Veronica</au><au>Chianese, Annalisa</au><au>Zannella, Carla</au><au>Franci, Gianluigi</au><au>De Filippis, Anna</au><au>Galdiero, Massimiliano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of antifungal spectrum of Cupferron against Candida albicans</atitle><jtitle>Microbial pathogenesis</jtitle><addtitle>Microb Pathog</addtitle><date>2024-09-01</date><risdate>2024</risdate><volume>194</volume><spage>106835</spage><pages>106835-</pages><artnum>106835</artnum><issn>0882-4010</issn><issn>1096-1208</issn><eissn>1096-1208</eissn><abstract>Candida albicans is an opportunistic yeast accounting for about 50–90 % of all cases of candidiasis in humans, ranging from superficial to systemic potentially life-threatening infections. The presence of several virulence factors, including biofilm, hyphal transition, and proteolytic enzymes production, worsens the fungal infections burden on healthcare system resources. Hence, developing new bioactive compounds with antifungal activity is a pressing urgence for the scientific community. In this perspective, we evaluated the anti-Candida potential of the N-Nitroso-N-phenylhydroxylamine ammonium salt (cupferron) against standard and clinical C. albicans strains. Firstly, the in vitro cytotoxicity of cupferron was checked in the range 400–12.5 μg/mL against human microglial cells (HMC-3). Secondly, its antifungal spectrum was explored via disk diffusion test, broth-microdilution method, and time-killing curve analysis, validating the obtained results through scanning electron microscopy (SEM) observations. Additionally, we evaluated the cupferron impact on the main virulence determinants of Candida albicans. At non-toxic concentrations (100–12.5 μg/mL), the compound exerted interesting anti-Candida activity, registering a minimum inhibitory concentration (MIC) between 50 and 100 μg/mL against the tested strains, with a fungistatic effect until 100 μg/mL. Furthermore, cupferron was able to counteract fungal virulence at MIC and sub-MIC values (50–12.5 μg/mL). These findings may propose cupferron as a new potential antifungal option for the treatment of Candida albicans infections.
•Antifungal evaluation of cupferron against planktonic and sessile Candida albicans.•Reduction of biofilm, hyphal transition and proteolytic enzymes production.•MIC at 50 μg/mL, with a fungistatic effect until 100 μg/mL.•The cytotoxicity in the range 100–12.5 μg/mL against HMC-3.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>39117014</pmid><doi>10.1016/j.micpath.2024.106835</doi><orcidid>https://orcid.org/0000-0003-3321-4331</orcidid><orcidid>https://orcid.org/0000-0001-7991-8700</orcidid><orcidid>https://orcid.org/0000-0002-7406-9882</orcidid><orcidid>https://orcid.org/0000-0002-1576-6290</orcidid><orcidid>https://orcid.org/0000-0002-1654-8500</orcidid><orcidid>https://orcid.org/0009-0000-5955-4495</orcidid><orcidid>https://orcid.org/0009-0004-8957-0719</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | ammonium salts Antifungal compound antifungal properties biofilm Candida albicans candidiasis Cupferron cytotoxicity disk diffusion antimicrobial test Drug-resistance electron microscopy health services humans hyphae minimum inhibitory concentration pathogenesis proteolysis Virulence yeasts |
title | Evaluation of antifungal spectrum of Cupferron against Candida albicans |
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