CHARacterization of natural products bioactivities in New Caledonian Marine microorganisms – CHARM

We will study effects of MNPs on drug resistant bacteria and immunomodulatory effects of host immune response during inflammatory phase. More specifically, microalgae extracts (MAEs) and marine bacteria exopolysaccharides (EPSs) will be tested towards drug-resistant bacterial strains isolated from the environment, from the territorial hospital center (CHT-NC) and from local patients, including Methicillin-resistant Staphylococcus aureus (MRSA), Ceftazidime-resistant Pseudomonas aeruginosa (CRPA), Vancomycin-resistant Enterococcus faecium (VRE) and Carbapenem-resistant Enterobacteriaceae (CRE). Antimicrobial activity of the MNPs will be determined by agars diffusion and microdilution methods. We will use in vitro models of induced human (PMA-treated THP-1 monocyte) and murine (RAW264.7 cells) macrophages to evaluate the potential regulation of major inflammatory cytokines using ELISA and RT-qPCR techniques. Inhibition of JAK-STAT signaling pathways will also be investigated using Western Blot and TransAM assays.

In progress

The project CHARM will investigate complementary bioactivities to identify innovative molecules to be proposed as platform molecules for pharmaceuticals in the field of antibacterial and immunomodulatory sectors, and results will be useful to improve the value-added chain in the field of MNPs and blue technology in New Caledonia. Thus, this project answers the need for a sustainable exploitation of marine bioresources and therefore contributes to the National Strategy for the Bioeconomy. It also contributes to the valorization of the biodiversity of the French Overseas and respond to the specification of the “Livre Bleu Outre-Mer” validated by the Ministry of Overseas. Long-term applications are expected in the sector of pharmaceutical industry with partnership with the private sector.

Expected

Context and objectives. Currently, 700,000 deaths are yearly attributed to antimicrobial resistance (AMR) in the world and this number is estimated to increase to 10 million by 2050. Indeed, the widespread use of antibiotics has led to the emergence of ‘superbugs’ such as Methicillin-resistant Staphylococcus aureus (MRSA) difficult to treat with existing medicines. This fosters the discovery of new efficient antibiotic treatments against severe human infectious diseases and related sepsis that is still associated with dramatic mortality rate. Immune-mediated inflammatory diseases (IMIDs) also represent a major global health issue with an incidence in Western society that approximates 5–7%. Cytokines are critical inflammatory mediators produced to trigger the host immune response during infections and are also major drivers of inflammatory response in IMIDs pathogenesis. Recent drug development focused on the regulation of inflammatory cytokines or on the inhibition of the Janus kinases (JAKs)/signal transducer and activator of transcription proteins (STATs) signaling pathways or Jakinibs approved for treatment of IMIDs. However, considering refractory patients and opportunistic diseases related to immunosuppressive mechanisms, drug developments are undergoing and focus on new molecules inhibiting cytokines or JAK-STAT signaling pathways. Marine microalgaes and bacteria produce anti-inflammatory and antimicrobial molecules of high pharmacological value. Bioprospecting campaigns in New Caledonia led to the characterization of microalgaes and marine bacteria producing bioactive molecules for blue biotechnology applications. We hypothesize novel bioactive marine natural products (MNPs) to be discovered from New Caledonian marine biodiversity and will characterize antibacterial and immunomodulatory MNPs from New Caledonian marine microalgaes and bacteria available from the collections of the IFREMER/ADECAL Technopole and the private start-up BIOTECAL. Brief methodological description. We will study effects of MNPs on drug resistant bacteria and immunomodulatory effects of host immune response during inflammatory phase. More specifically, microalgae extracts (MAEs) and marine bacteria exopolysaccharides (EPSs) will be tested towards drug-resistant bacterial strains isolated from the environment, from the territorial hospital center (CHT-NC) and from local patients, including Methicillin-resistant Staphylococcus aureus (MRSA), Ceftazidime-resistant Pseudomonas aeruginosa (CRPA), Vancomycin-resistant Enterococcus faecium (VRE) and Carbapenem-resistant Enterobacteriaceae (CRE). Antimicrobial activity of the MNPs will be determined by agars diffusion and microdilution methods. We will use in vitro models of induced human (PMA-treated THP-1 monocyte) and murine (RAW264.7 cells) macrophages to evaluate the potential regulation of major inflammatory cytokines using ELISA and RT-qPCR techniques. Inhibition of JAK-STAT signaling pathways will also be investigated using Western Blot and TransAM assays. Expected impacts of the project. The project CHARM will investigate complementary bioactivities to identify innovative molecules to be proposed as platform molecules for pharmaceuticals in the field of antibacterial and immunomodulatory sectors, and results will be useful to improve the value-added chain in the field of MNPs and blue technology in New Caledonia. Thus, this project answers the need for a sustainable exploitation of marine bioresources and therefore contributes to the National Strategy for the Bioeconomy. It also contributes to the valorization of the biodiversity of the French Overseas and respond to the specification of the “Livre Bleu Outre-Mer” validated by the Ministry of Overseas. Long-term applications are expected in the sector of pharmaceutical industry with partnership with the private sector.