title: Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum.
abstract: Superficial mycoses caused by dermatophytic fungi such as Trichophyton rubrum represent the most common type of worldwide human infection affecting various keratinized tissues in our body such as the skin, hair, and nails, etc. The dermatophytic infection is a significant public health threat due to its persistent nature and high recurrence rates, and thus alternative treatments to cure this fungal infection are urgently required. The present study mainly focused on the synergistic activity of violacein with four azole drugs (ketoconazole, fluconazole, clotrimazole, and itraconazole) against T. rubrum. The synergistic antifungal activities of violacein and azoles were measured by checkerboard microdilution and time-kill assays. In our study, combinations of violacein and azoles predominantly recorded synergistic effect (FIC index < 0.5). Significant synergistic value was recorded by the combination of violacein and clotrimazole. Time-kill assay by the combination of MIC concentration of violacein and azoles recorded that the growth of the T. rubrum was significantly arrested after 4-12 h of treatment. The combination of violacein and azoles leads to the enhanced inhibition of mycelial growth and conidial germination. Moreover combination enhanced the rate of release of intracellular materials. Morphological changes by SEM analysis were also prominent with the combination. A normal human cell line [Foreskin (FS) normal fibroblast] was used to check the cytotoxicity of violacein. Interestingly violacein recorded no cytotoxicity up to 100 μg/ml. The in vitro synergistic effect of violacein and azoles against clinically relevant fungi, T. rubrum, is reported here for the first time. Finally, our findings support the potential use of the violacein as an antifungal agent especially against dermatophytic fungi T. rubrum.
authors: Environmental Technology, CSIR-National Institute for Interdisciplinary Science and Technology Thiruvananthapuram, India.
authors: S
authors: S
authors: Anju
authors: Agroprocessing and Natural Products Division, CSIR-National Institute for Interdisciplinary Science and Technology Thiruvananthapuram, India.
authors: Nishanth S
authors: NS
authors: Kumar
authors: Environmental Technology, CSIR-National Institute for Interdisciplinary Science and Technology Thiruvananthapuram, India.
authors: B
authors: B
authors: Krishnakumar
authors: Agroprocessing and Natural Products Division, CSIR-National Institute for Interdisciplinary Science and Technology Thiruvananthapuram, India.
authors: B S Dileep
authors: BS
authors: Kumar
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology* / Q000633:toxicity; D001393:Azoles / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D025282:Mycelium / Q000187:drug effects / Q000254:growth & development; D013172:Spores, Fungal / Q000187:drug effects / Q000254:growth & development; D013997:Time Factors; D014249:Trichophyton / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology / Q000648:ultrastructure
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D007211:Indoles; C063155:violacein
keywords: Trichophyton rubrum; azoles; dermatophytosis; synergistic; violacein