Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis
The ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (no...
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1402 |
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| author | Caroline B. Costa-Orlandi Níura M. Bila Jean Lucas C. Bonatti Carolina O. Vaso Mariana B. Santos Carlos R. Polaquini Mariana M. Santoni Biasioli Rondinelli D. Herculano Luis O. Regasini Ana Marisa Fusco-Almeida Maria José S. Mendes-Giannini |
| author_facet | Caroline B. Costa-Orlandi Níura M. Bila Jean Lucas C. Bonatti Carolina O. Vaso Mariana B. Santos Carlos R. Polaquini Mariana M. Santoni Biasioli Rondinelli D. Herculano Luis O. Regasini Ana Marisa Fusco-Almeida Maria José S. Mendes-Giannini |
| author_sort | Caroline B. Costa-Orlandi |
| collection | DOAJ |
| description | The ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action on planktonic cells and biofilms of <i>T. rubrum</i> and <i>T. mentagrophytes</i>. Metabolic activities, ergosterol, and reactive oxygen species (ROS) were quantified, and the expression of genes encoding ergosterol was determined by real-time PCR. The effects on the biofilm structure were visualized using confocal electron microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). <i>T. rubrum</i> and <i>T. mentagrophytes</i> biofilms were susceptible to nonyl and resistant to fluconazole, griseofulvin (all strains), and terbinafine (two strains). The SEM results revealed that nonyl groups seriously damaged the biofilms, whereas synthetic drugs caused little or no damage and, in some cases, stimulated the development of resistance structures. Confocal microscopy showed a drastic reduction in biofilm thickness, and transmission electron microscopy results indicated that the compound promoted the derangement and formation of pores in the plasma membrane. Biochemical and molecular assays indicated that fungal membrane ergosterol is a nonyl target. These findings show that nonyl 3,4-dihydroxybenzoate is a promising antifungal compound. |
| first_indexed | 2024-03-11T03:24:57Z |
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| id | doaj.art-fe8a1dcf3ccb44f9928dd22deb32b1b4 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:57Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-fe8a1dcf3ccb44f9928dd22deb32b1b42023-11-18T02:51:04ZengMDPI AGPharmaceutics1999-49232023-05-01155140210.3390/pharmaceutics15051402Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of DermatophytosisCaroline B. Costa-Orlandi0Níura M. Bila1Jean Lucas C. Bonatti2Carolina O. Vaso3Mariana B. Santos4Carlos R. Polaquini5Mariana M. Santoni Biasioli6Rondinelli D. Herculano7Luis O. Regasini8Ana Marisa Fusco-Almeida9Maria José S. Mendes-Giannini10Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (U.N.E.S.P.), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (U.N.E.S.P.), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (U.N.E.S.P.), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (U.N.E.S.P.), Araraquara 14800-903, SP, BrazilDepartment of Chemistry and Environmental Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (U.N.E.S.P.), Sao Jose do Rio Preto 15054-000, SP, BrazilDepartment of Chemistry and Environmental Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (U.N.E.S.P.), Sao Jose do Rio Preto 15054-000, SP, BrazilDepartment of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (U.N.E.S.P.), Araraquara 14800-903, SP, BrazilDepartment of Bioprocesses and Biotechnology, School of Pharmaceutical Sciences, São Paulo State University (U.N.E.S.P.), Araraquara 14800-903, SP, BrazilDepartment of Chemistry and Environmental Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (U.N.E.S.P.), Sao Jose do Rio Preto 15054-000, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (U.N.E.S.P.), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (U.N.E.S.P.), Araraquara 14800-903, SP, BrazilThe ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action on planktonic cells and biofilms of <i>T. rubrum</i> and <i>T. mentagrophytes</i>. Metabolic activities, ergosterol, and reactive oxygen species (ROS) were quantified, and the expression of genes encoding ergosterol was determined by real-time PCR. The effects on the biofilm structure were visualized using confocal electron microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). <i>T. rubrum</i> and <i>T. mentagrophytes</i> biofilms were susceptible to nonyl and resistant to fluconazole, griseofulvin (all strains), and terbinafine (two strains). The SEM results revealed that nonyl groups seriously damaged the biofilms, whereas synthetic drugs caused little or no damage and, in some cases, stimulated the development of resistance structures. Confocal microscopy showed a drastic reduction in biofilm thickness, and transmission electron microscopy results indicated that the compound promoted the derangement and formation of pores in the plasma membrane. Biochemical and molecular assays indicated that fungal membrane ergosterol is a nonyl target. These findings show that nonyl 3,4-dihydroxybenzoate is a promising antifungal compound.https://www.mdpi.com/1999-4923/15/5/1402dermatophytesbiofilmsanti-biofilm activityantifungal drugsmechanism of actionRT-PCR |
| spellingShingle | Caroline B. Costa-Orlandi Níura M. Bila Jean Lucas C. Bonatti Carolina O. Vaso Mariana B. Santos Carlos R. Polaquini Mariana M. Santoni Biasioli Rondinelli D. Herculano Luis O. Regasini Ana Marisa Fusco-Almeida Maria José S. Mendes-Giannini Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis Pharmaceutics dermatophytes biofilms anti-biofilm activity antifungal drugs mechanism of action RT-PCR |
| title | Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis |
| title_full | Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis |
| title_fullStr | Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis |
| title_full_unstemmed | Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis |
| title_short | Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis |
| title_sort | membranolytic activity profile of nonyl 3 4 dihydroxybenzoate a new anti biofilm compound for the treatment of dermatophytosis |
| topic | dermatophytes biofilms anti-biofilm activity antifungal drugs mechanism of action RT-PCR |
| url | https://www.mdpi.com/1999-4923/15/5/1402 |
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