title: Tramadol, an Opioid Receptor Agonist: An Inhibitor of Growth, Morphogenesis, and Biofilm Formation in the Human Pathogen, Candida albicans.
abstract: Tramadol is a synthetic, centrally acting low-affinity agonist of μ-opioid receptors in humans. It is used as an analgesic and is shown to have local anesthetic action. In this study, we have tried to explore its anti-Candida potential. Minimum inhibitory concentration (MIC50) and minimum fungicidal concentration (MFC) values were established. MIC50 ranged from 2 to 4 mg/mL, whereas MFC was recorded at 8 mg/mL. Also, the effect of tramadol on germ tube formation, adhesion, and biofilms in Candida albicans was studied. Tramadol impaired in vitro growth of C. albicans. A time-dependent killing assay showed that it kills C. albicans within 24 h of exposure. Tramadol has strong activity against Candida virulence factors such as yeast-to-hyphal form switching and adhesion. C. albicans biofilms, which are notoriously resistant to many antifungals, were sensitive to tramadol. At 8 mg/mL of tramadol, 82% of early stage biofilms and 52.88% of matured biofilms were inhibited. Although our results show that the antifungal effect of tramadol requires concentrations that can be achieved only locally, they may provide potential candidates for development of novel antifungal drugs.
authors.affiliation: 1 Department of Microbiology, Savitribai Phule Pune Unversity , Pune, India .
authors.forename: Gunderao Hanumantrao
authors.initials: GH
authors.lastname: Kathwate
authors.affiliation: 2 DST-FIST and UGC-SAP Sponsored School of Life Sciences, SRTM University , Nanded, India .
authors.forename: S Mohan
authors.initials: SM
authors.lastname: Karuppayil
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D009024:Morphogenesis / Q000187:drug effects* / Q000502:physiology; D014147:Tramadol / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D000935:Antifungal Agents; D014147:Tramadol
keywords: Candida albicans; antifungals; biofilm and drug development; tramadol