title: Synergistic activity of phenazines isolated from Pseudomonas aeruginosa in combination with azoles against Candida species.
abstract: Candidiasis infections are caused by yeasts from the genus Candida. The types of infection range from superficial to systemic. Treatment often requires antifungals such as the azoles; however, increased use of these drugs has led to the generation of yeasts with increased resistance to these drugs. Here, we describe the synergistic anticandidal activity of three phenazines-phenazine-1-ol, phenazine-1-carboxylic acid, and phenazine-1-carboxamide. These phenazines were purified from Pseudomonas aeruginosa in combination with three clinically used azoles-fluconazole, itraconazole, and clotrimazole. The synergistic anticandidal activities of phenazines and azoles were assessed using the checkerboard microdilution and time-kill methods. Study results show that the combined effects of phenazines and azoles were predominantly synergistic activity (fractional inhibitory concentration index <0.5). The time-kill study, which included a combination of the minimum inhibitory concentration of phenazines and azoles, showed growth of Candida species that was completely attenuated after 0-6 h of treatment. These results, which suggest that the activity of phenazines and azoles may be beneficial, have potential implications in delaying the development of resistance, as the anticandidal effect is achieved with lower concentrations of both agents (phenazines and azoles). The cytotoxicity of phenazines was also tested against a normal human cell line (foreskin normal fibroblast). No cytotoxicity was recorded at concentrations up to 200 μg/ml. The in vitro synergistic activity of phenazines and azoles against Candida species is reported here for the first time.
authors.affiliation: Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvanathapuram 695 019, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Nishanth Kumar
authors.affiliation: Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvanathapuram 695 019, Kerala, India.
authors.forename: G V
authors.initials: GV
authors.lastname: Nisha
authors.affiliation: Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvanathapuram 695 019, Kerala, India.
authors.forename: A
authors.initials: A
authors.lastname: Sudaresan
authors.affiliation: Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvanathapuram 695 019, Kerala, India.
authors.forename: V V
authors.initials: VV
authors.lastname: Venugopal
authors.affiliation: Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvanathapuram 695 019, Kerala, India.
authors.forename: M M
authors.initials: MM
authors.lastname: Sree Kumar
authors.affiliation: Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvanathapuram 695 019, Kerala, India.
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Lankalapalli
authors.affiliation: Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvanathapuram 695 019, Kerala, India kumardileep@niist.res.in micronishanth@rediffmail.com.
authors.forename: B S
authors.initials: BS
authors.lastname: Dileep Kumar
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D002460:Cell Line; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010619:Phenazines / Q000302:isolation & purification / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D010619:Phenazines
keywords: Candida species; azoles; phenazines; synergistic