Studies on the antifungal and serotonin receptor agonist activities of the secondary metabolites from piezotolerant deep-sea fungusAscotrichasp.

Abstract

The potent antifungal agent sesquiterpenes and serotonin 5-HT 2C agonist ascotricin were produced by a newly isolated deep-sea fungus Ascotricha sp. This fungus was isolated from deep-sea sediment collected at a depth of 1235 m and characterized. Piezotolerance was successfully tested under high pressure-low temperature (100 bar pressure and 20ºC) microbial cultivation system. Production of secondary metabolites was enhanced at optimized culture conditions. The in-vivo antifungal activity of sesquiterpenes was studied using the Caenorhabditis elegans-Candida albicans model system. The sesquiterpenes affected the virulence of C. albicans and prolonged the life of the host C. elegans. These findings suggest that sesquiterpenes are attractive antifungal drug candidates. The 5-HT 2C receptor agonist is a potential target for the development of drugs for a range of central nervous system disorders. The interaction of 5-HT 2C agonist ascotricin with the receptor was studied through bioinformatic analysis. The in silico molecular docking and molecular dynamic simulation studies demonstrated that they fit into the serotonin 5-HT 2C active site and the crucial amino acid residues involved in the interactions were identified. To our knowledge, this is first report of in vivo antifungal analysis of sesquiterpenes and in silico studies of serotonin 5-HT 2C receptor-ascotricin complex.

Caenorhabditis elegans as an Infection Model for Pathogenic Mold and Dimorphic Fungi: Applications and Challenges

“…C. elegans glp-4; sek-1 worms have mostly been used in these studies (aside from the wildtype strain, N2) because of their inability to produce progeny at 25°C due to the glp-4 mutation and their susceptibility to pathogens due to sek-1 mutation, thus making the worms immunocompromised for infection by opportunistic human fungi (Huang et al, 2014;Okoli and Bignell, 2015;Ahamefule et al, 2020a) Moreover, the adoption of a C. elegans model for searching and screening of effective bioactive compounds against several species of Candida has also received much attention. Effective bioactive compounds from marine habitats (Subramenium et al, 2017;Ganesh Kumar et al, 2019), plant parts (Shu et al, 2016;Pedroso et al, 2019), and other sources (Table 2) have been discovered because of their in vivo efficacies against several Candida species and were simultaneously evaluated for their cytotoxicity in a C. elegans model. Compounds such as alizarin, chrysazin, sesquiterpene, and purpurin were discovered to be quite effective in in vivo assays with effective doses ranging from 1 to 10 µg/ml (Table 2), indicating potential future prospects for antifungal drug research and discovery.…”