MYCOSEAS
"Production and characterization of new bioactive molecules against emerging and/or multidrug-resistant pathogens by neglected poly-extremophilic marine fungi"
MYCOSEAS is financed by the E.U “Next Generation EU” by the PRIN 2022 framework (Project n°: 2022MPTT35)
ABSTRACT
Lot of medical problems are caused by microbial diseases for which treatment is still unavailable. Also, emerging and re-emerging pathogens represent great increasing medical and social concerns. Among them we can list new or scarcely studied viruses, bacteria and fungi. In addition, widely increasing problems are due to known microbes that acquired resistance or multi-resistance to conventional antibiotics; some of them cause further problems since they are involved in the production of biofilms causing various medical issues. This constantly change the landscape of clinical microbiology that requires new therapeutic strategies and molecules.
Marine environment has several characteristics leading to the discovery of new microbial strains, having unique features, that can be exploited for new bioactive molecules. Marine fungi, are a diversified source of bioactive metabolites that could be potentially used as new drugs. They are somehow underrated and their chemical and biological diversity is still underestimated. Many new or little studied (neglected species) taxa need to be carefully investigated to search new bioactive metabolites.
In this project (see graphical abstract) selected marine fungi, will be studied for their production of new secondary metabolites (SMs) active against emerging pathogens (virus, bacteria and fungi) also within biofilm matrixes. Among the various strains stored in the culture collections of marine fungi, managed by the project participants, 30 strains will be selected for their characteristic to belong to new or neglected species and possibly showing poly-extremophilic features. The selected fungi will be screened to individuate those with possible high production of SMs. Screening, targeting secondary metabolism genes (NRPS, PKS, TS) will allow to select a maximum of 10 strains for the subsequent work steps. To stimulate the expression of silent secondary metabolite genes, according to the OSMAC strategy, the selected fungi will be cultivated on various solid and liquid media under different chemico-physical growth conditions. Culture extracts will be tested for their antiviral, antimicrobial and antibiofilm activity. Active extracts will be analysed by metabolomic techniques in order to get a metabolic network relating metabolite production and culture conditions. For best promising strains, production of SMs will be upscaled to obtain sufficient material for further activity tests and for bioactive molecule isolation and characterization. Positive extracts will be fractionated to get a library of enriched fractions to be used in the activity tests. Isolation and purification of bioactive compounds will allow to determine their chemical structure. Purified bioactive molecules will be tested for their biological activity too.