SESAM

The chemistry of sponge specialized metabolites (SpMs) has been extensively studied in the fields of anti-cancer and to a lesser extent anti-microbial drug discovery. The shrinking therapeutic choice for the treatment of multi-resistant bacterial infections or emerging viral infections, collectively underlines the necessity to maintain anti-microbial drug discovery endeavors. In that regards, sponge SpMs have displayed interesting anti-microbial properties, which are still relatively underexplored. Structurally complex, these SpMs are often purified in low yields. In some cases, massive harvests of sponge biomass were performed to obtain the most promising SpMs in sufficient quantities, thereby fragilizing the marine ecosystem. Clearly, the sustainable valorization of the chemical and biological potentials of marine SpMs should come hand in gloves with the implementation of eco-responsible supply methods. Interestingly, sponges can release part of their SpMs into their surroundings (exo-SpMs) through the renewal or active expulsion of their cells. These exo-SpMs represent a source of bioactive molecules, which could be collected and concentrated from seawater without destroying the sponge biomass, thus, without affecting marine biodiversity. In this context, the SESAM project aims at (1) characterizing the chemical and biological properties of exo-SpMs, and (2) valorizing them as an additional and sustainable source of new antimicrobials. An interdisciplinary approach will be developed to characterize the cells involved in the production and expulsion of exo-SpMs (AIM1), to develop efficient methods for concentrating exo-SpMs in aquaria and marine environments (AIM2), and to evaluate both their antibiotic properties against ESKAPE bacteria, and their antiviral activities against Dengue and Zika Flaviviruses (AIM3). This project, thus, brings together experts from different scientific fields: sponge biology and ecology, cellular and molecular biology, natural product chemistry, and microbiology. The SESAM team will study the chemical and antimicrobial properties of exo-SpMs from selected Mediterranean sponge species that contain different types of specialized cells possibly involved in the production and release of SpMs, all belonging to the alkaloid structural class. High-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) will be used for comparative metabolomic analyses and for the structural elucidation of isolated SpMs. Symbiotic cells (microorganisms and specialized sponge cells), isolated from the sponge biomass but also excreted in aquaria, will be identified by DNA metabarcode and microscopy techniques. The antibiotic and antiviral activities of sponge extracts, cellular fractions, and isolated SpMs will be measured on the renowned screening platforms (BAC-SCREEN and AFMB) of Aix Marseille University. In the mid-to long terms, this project will lead to further development of techniques for a durable production and/or concentration of promising exo-SpMs. Additionally, data and results collected during this project will contribute to better characterize the ecosystemic functions of sponge exo-metabolites. Hence, this project combines marine chemical ecology with eco-responsible natural product drug discoveries. Thanks to its unique interdisciplinary approach, the SESAM project sets the ground foundation for evaluating all parameters involved in determining sponge exo-SpMs as a sustainable source of bioactive compounds.