Possible mechanism of antifungal phenazine‐1‐carboxamide from Pseudomonas sp. against dimorphic fungi Benjaminiella poitrasii and human pathogen Candida albicans

• Published in: Journal of applied microbiology 2015, Vol.118 (1), p.39-48
• Main Authors: Tupe, S.G, Kulkarni, R.R, Shirazi, F, Sant, D.G, Joshi, S.P, Deshpande, M.V
• Format: Article
• Language: English
• Subjects: Antifungal Agents - pharmacology; antifungal properties; Apoptosis; Aspergillus fumigatus; Aspergillus niger; Benjaminiella; Candida albicans; Candida albicans - drug effects; Candida glabrata; chromatin; Cryptococcus neoformans; death; dimorphism; DNA fragmentation; fluorescence; Fungi; Fusarium oxysporum; germ tube; humans; metabolites; Microbiology; mitochondrial membrane; Mucorales - drug effects; Mucorales - metabolism; Pathogens; phenazines; Phenazines - isolation & purification; Phenazines - pharmacology; phosphatidylserines; Pseudomonas; Pseudomonas - chemistry; Pseudomonas sp; reactive oxygen species; Reactive Oxygen Species - metabolism; yeasts
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/jam.12675

AIM: Investigation of antifungal mechanism of phenazine 1‐carboxamide (PC) produced by a Pseudomonas strain MCC2142. METHODS AND RESULTS: An antifungal metabolite produced by a Pseudomonas was purified and identified as PC. Human pathogenic fungi such as Candida albicans, Candida glabrata, Cryptococcus neoformans, Fusarium oxysporum, Aspergillus fumigatus and Aspergillus niger were found to be inhibited by PC (MIC₉₀32–64 μg ml⁻¹). Addition of PC (20 μg ml⁻¹) during yeast (Y)–hypha (H) transitions inhibited germ tube formation by >90% and >99% in C. albicans National Collection of Industrial Microorganisms (NCIM) 3471 and nonpathogenic model Benjaminiella poitrasii, respectively. After exposure to PC (20 μg ml⁻¹), 75–80% yeast cells of B. poitrasii and C. albicans NCIM 3471 showed rhodamine 123 fluorescence indicating high intracellular reactive oxygen species (ROS) production. ROS further led to hyperpolarization of mitochondrial membrane, subsequently induction of apoptosis as evident by externalization of phosphatidylserine, DNA fragmentation, chromatin condensation and finally death in B. poitrasii. In C. albicans NCIM 3471, PC (20 μg ml⁻¹) induced apoptosis. CONCLUSIONS: The antifungal effect of PC in B. poitrasii and C. albicans may be due to ROS‐mediated apoptotic death. SIGNIFICANCE AND IMPACT OF THE STUDY: Inhibition of Y–H transition of B. poitrasii and C. albicans by PC indicates that it may prove useful in the control of dimorphic human pathogens.