Melisa A Quinteros1,2,3, Ivana L D Galera1,3, Juan Tolosa4, Joaquín C García-Martínez4, Paulina L Páez2,3,5, María G Paraje1,3. 1. IMBIV - CONICET, Córdoba, Argentina. 2. Departamento de Cs. Farmacéuticas, Fac. de Cs. Químicas, Univ. Nacional de Córdoba, Argentina. 3. Cátedra de Microbiología, Fac. de Cs. Exactas Físicas y Naturales, Univ. Nacional de Córdoba, Argentina. 4. Fac. de Farmacia de Albacete, Centro Regional de Inv. Biomédicas, Univ. de Castilla-La Mancha, España. 5. UNITEFA - CONICET, Córdoba, Argentina.
Abstract
As sessile cells of fungal biofilms are at least 500-fold more resistant to antifungal drugs than their planktonic counterparts, there is a requirement for new antifungal agents. Olygostyrylbenzenes (OSBs) are the first generation of poly(phenylene)vinylene dendrimers with a gram-positive antibacterial activity. Thus, this study aimed to investigate the antifungal activity of four OSBs (1, 2, 3, and 4) on planktonic cells and biofilms of Candida tropicalis. The minimum inhibitory concentration (MIC) for the planktonic population and the sessile minimum inhibitory concentrations (SMIC) were determined. Biofilm eradication was studied by crystal violet stain and light microscopy (LM), and confocal laser scanning microscopy (CLSM) was also utilized in conjunction with the image analysis software COMSTAT. Although all the OSBs studied had antifungal activity, the cationic OSBs were more effective than the anionic ones. A significant reduction of biofilms was observed at MIC and supraMIC50 (50 times higher than MIC) for compound 2, and at supraMIC50 with compound 3. Alterations in surface topography and the three-dimensional architecture of the biofilms were evident with LM and CLSM. The LM analysis revealed that the C. tropicalis strain produced a striking biofilm with oval blastospores, pseudohyphae, and true hyphae. CLSM images showed that a decrease occurred in the thickness of the mature biofilms treated with the OSBs at the most effective concentration for each one. The results obtained by microscopy were supported by those of the COMSTAT program. Our results revealed an antibiofilm activity, with compound 2 being a potential candidate for the treatment of C. tropicalis infections. LAY SUMMARY: This study aimed to investigate the antifungal activity of four OSBs (1, 2, 3, and 4) on planktonic cells and biofilms of Candida tropicalis. Our results revealed an antibiofilm activity, with compound 2 being a potential candidate for the treatment of C. tropicalis infections.
As sessile cells of fungal biofilms are at least 500-fold more resistant to antifungal drugs than their planktonic counterparts, there is a requirement for new antifungal agents. Olygostyrylbenzenes (OSBs) are the first generation of poly(phenylene)vinylene dendrimers with a gram-positive antibacterial activity. Thus, this study aimed to investigate the antifungal activity of four OSBs (1, 2, 3, and 4) on planktonic cells and biofilms of Candida tropicalis. The minimum inhibitory concentration (MIC) for the planktonic population and the sessile minimum inhibitory concentrations (SMIC) were determined. Biofilm eradication was studied by crystal violet stain and light microscopy (LM), and confocal laser scanning microscopy (CLSM) was also utilized in conjunction with the image analysis software COMSTAT. Although all the OSBs studied had antifungal activity, the cationic OSBs were more effective than the anionic ones. A significant reduction of biofilms was observed at MIC and supraMIC50 (50 times higher than MIC) for compound 2, and at supraMIC50 with compound 3. Alterations in surface topography and the three-dimensional architecture of the biofilms were evident with LM and CLSM. The LM analysis revealed that the C. tropicalis strain produced a striking biofilm with oval blastospores, pseudohyphae, and true hyphae. CLSM images showed that a decrease occurred in the thickness of the mature biofilms treated with the OSBs at the most effective concentration for each one. The results obtained by microscopy were supported by those of the COMSTAT program. Our results revealed an antibiofilm activity, with compound 2 being a potential candidate for the treatment of C. tropicalis infections. LAY SUMMARY: This study aimed to investigate the antifungal activity of four OSBs (1, 2, 3, and 4) on planktonic cells and biofilms of Candida tropicalis. Our results revealed an antibiofilm activity, with compound 2 being a potential candidate for the treatment of C. tropicalis infections.