Co-culturing of Fungal Strains Against Botrytis cinerea as a Model for the Induction of Chemical Diversity and Therapeutic Agents

Abstract

New fungal SMs (SMs) have been successfully described to be produced by means of in vitro-simulated microbial community interactions. Co-culturing of fungi has proved to be an efficient way to induce cell–cell interactions that can promote the activation of cryptic pathways, frequently silent when the strains are grown in laboratory conditions. Filamentous fungi represent one of the most diverse microbial groups known to produce bioactive natural products. Triggering the production of novel antifungal compounds in fungi could respond to the current needs to fight health compromising pathogens and provide new therapeutic solutions. In this study, we have selected the fungus Botrytis cinerea as a model to establish microbial interactions with a large set of fungal strains related to ecosystems where they can coexist with this phytopathogen, and to generate a collection of extracts, obtained from their antagonic microbial interactions and potentially containing new bioactive compounds. The antifungal specificity of the extracts containing compounds induced after B. cinerea interaction was determined against two human fungal pathogens (Candida albicans and Aspergillus fumigatus) and three phytopathogens (Colletotrichum acutatum, Fusarium proliferatum, and Magnaporthe grisea). In addition, their cytotoxicity was also evaluated against the human hepatocellular carcinoma cell line (HepG2). We have identified by LC-MS the production of a wide variety of known compounds induced from these fungal interactions, as well as novel molecules that support the potential of this approach to generate new chemical diversity and possible new therapeutic agents.

Fungal Pigments and Their Prospects in Different Industries

“…Nowadays, co-culturing has been found to be an effective method for the activation of cryptic pathways via cell-cell interactions, which ultimately results in the production of novel secondary metabolites such as pigments from the fungi [168,169]. Studies have reported that the induction or enhancement in pigment production was possible using co-culturing of fungi with bacteria or yeast, but it was species-specific.…”

Molecular Networking-Based Metabolome and Bioactivity Analyses of Marine-Adapted Fungi Co-cultivated With Phytopathogens

“…This competitive nature renders phytopathogens promising model organisms and challengers in co-cultivation studies. A recent co-cultivation study between the phytopathogenic fungus B. cinerea and a wide variety of fungi from different environments led to the discovery of novel antifungal compounds ( Serrano et al, 2017 ). In another example, the frosty pod rot cocoa disease-causing fungus, Moniliophthora roreri , elicited the production of the antifungal agents T39 butenolide, harzianolide, and sorbicillinol in Trichoderma harzianum ( Tata et al, 2015 ).…”

Design of Fungal Co-Cultivation Based on Comparative Metabolomics and Bioactivity for Discovery of Marine Fungal Agrochemicals

“…and P. influorescens) displayed patterns of distance inhibition. This pattern is associated with the release of antimicrobial molecules into the medium to inhibit competitors [35,36]. In contrast, the co-culture of the weak candidates (P. nobilis and Lentithecium sp.)…”