Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis

• Príomhchruthaitheoirí: Caroline B. Costa-Orlandi (Údar), Níura M. Bila (Údar), Jean Lucas C. Bonatti (Údar), Carolina O. Vaso (Údar), Mariana B. Santos (Údar), Carlos R. Polaquini (Údar), Mariana M. Santoni Biasioli (Údar), Rondinelli D. Herculano (Údar), Luis O. Regasini (Údar), Ana Marisa Fusco-Almeida (Údar), Maria José S. Mendes-Giannini (Údar)
• Formáid: LEABHAR
• Foilsithe / Cruthaithe: MDPI AG, 2023-05-01T00:00:00Z.
• Ábhair: article
• Rochtain ar líne: Connect to this object online.
• Notes: 10.3390/pharmaceutics15051402; 1999-4923
• Keywords: dermatophytes; biofilms; anti-biofilm activity; antifungal drugs; mechanism of action; RT-PCR; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 15, Iss 5, p 1402 (2023)

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.