SESAM : Valorizing Sponge Exometabolites as Sustainable Source of AntiMicrobials

Abstract

The chemistry of sponges specialized metabolites (SpM) has been extensively studied in the fields of anti-cancer and anti-infectious drug discovery. However, most of the biological investigations carried out with promising sponge SpMs have been hampered by a general supply issue. Interestingly, sponge SpMs can be released in its surroundings either through cellular turnover or active cell expulsion, thus leading to the production of an exo-metabolome. This project aims at evaluating the sustainability of sponge exo-metabolites as source of bioactive new antimicrobials that could be collected without destroying the sponge biomass. Hence, a multi-disciplinary approach with innovative techniques will be developed (1) to characterize both excreted cells and exo-SpMs from Mediterranean sponges maintained in aquarium, and (2) to compare the antimicrobial properties of excreted and non-excreted SpMs.
This project will further advance eco-responsible marine drug discovery endeavors.

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Challenge
Accessing sponge chemo-diversity & valorizing their antimicrobial potentials in an eco-responsible way, while preserving marine biodiversity.

Objectives

An interdisciplinary approach with innovative techniques is proposed to evaluate the sustainability of sponge exo-SpMs as source of antibiotics against multi-drug resistant bacteria and/or antiviral agents against certain Flaviviruses (arthropod, i.e mosquitoes/ticks, born infections). The three aims of this project are :

  • AIM 1 : isolate sponge cells and characterize their SpM composition.
  • AIM 2 : develop methods to concentrate exo-SpMs and sponge cells.
  • AIM 3 : compare the anti-microbial properties of excreted and non-excreted SpMs on dedicated high-throughput screening platforms at Aix-Marseille University.

Project Organization

This project is organized in 6 tasks distributed between the three aims as illustrated in the figure below.

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  • Task 1 involves the project coordination and communication activities.
  • Task 2 encompasses all activities related to sponge collections.
  • Task 3 will focus on the sponge cell separation and identification using microscopic and DNA metabarcoding analyses
  • Task 4 is dedicated to the development of methods to capture and concentrate sponge exo-metabolomes.
  • Task 5 is associated with the comparison of the antimicrobial properties of excreted and non-excreted sponge metabolites.
  • Task 6 comprises all the comparative chemical analyses. The isolation and structural identification/verification of potentially novel exo-SpMs will be initiated in this Task.

Team members

Members of the SESAM team are part of the DFME team 5 and the IMBE joint resources. Highly interdisciplinary, the SESAM team is composed of specialists in sponge biology, marine ecology, and natural product chemistry.

Members associated with the DFME team

  1. Charlotte Simmler, CR CNRS
  2. Thierry Pérez DR CNRS
  3. Pierre Chevaldonné, DR CNRS
  4. Alexander Ereskovsky, DR CNRS
  5. Béatrice Baghdikian, MC, HDR AMU
  6. Mathieu Santonja, MC AMU
  7. Morgane Mauduit, engineer in Chemistry, PhD student (November 1st 2020, October 31, 2023 CNRS fellowship
  • And soon new young researchers (post-doc and PhD students) will join the team. Stay tuned !

Members associated with the Joint Research Resources

  1. Stéphane Greff, IGE AMU, co-managing the metabolomics and chemical ecology MALLABAR joint resource, UPLC-MS
  2. Caroline Lecareux, IE AMU, co-managing the metabolomics and chemical ecology MALLABAR joint resource, GC-MS
  3. Sacha Molinari, TCN CNRS, metabolomics and chemical ecology MALLABAR, joint resource
  4. Caroline Rocher, AI CNRS, technical coordination of the molecular biology joint resource

Collaborations within Aix Marseille University

Antibiotic assays on the BAC-SCREEN antibiotic screening platform (UMR INSERM U1261 Jean-Michel Bolla, Véronique Sinou) : testing for the anti-bacterial properties of sponge extracts and molecules on multi-resistant bacteria.

Antiviral Assays on the Marseille Luminy Screening Platform (PCML, UMR CNRS 7257 Jean-Claude Guillemot, Cecilia Eydoux) : assessing the capacities of sponge extracts and their molecules to inhibit the replication of Flaviviruses.

NMR and structure analyses : Gaëtan Herbette (Spectropole, FR1739 /) and Oliver Bornet (IMM, FR3479 ).

Fundings


Agence Nationale de la Recherche (ANR)

ANR JCJC (Jeune Chercheur) : ANR-20-CE43-0003

Amount : 331 525 €
Project duration : 4 years

(1st February 2021-31 January 2025)

Scientific coordinator : Charlotte Simmler
Research Site : Station Marine d’Endoume