Biotechnology company Nosopharm has signed a collaboration agreement with the DGIMI laboratory (UMR1333: Diversity, Genomes and Insects-Microorganisms Interactions), with the aim of producing chemical libraries of bioactive molecules for the company’s anti-infective screening campaigns against antibiotic resistance.
DGIMI falls under the authority of the French National Research Institute for Agriculture, Food, and the Environment (INRAE) and the University of Montpellier. ‘France Relance’, the French government’s investment plan created following the COVID-19 pandemic, will provide financial support for the collaboration.
The partners have set up a research strategy with a view to cataloguing the specialised bioactive metabolites produced by the bacteria strains Photorhabdus and Xenorhabdus, as well as by strains frequently associated with them (microbiota of entomopathogenic nematodes), regardless of their biological activity. The metabolites will be grouped into libraries compatible with biological activity screenings used to identify their potential applications for human, animal and plant health.
The production of specialised bioactive microbial metabolites is said to be linked to the presence of biosynthetic gene clusters (BGCs) in the genomes of microorganisms. Although many BGCs have been identified in certain strains of bacteria, little is known about the chemical structures and biological activity of the metabolites associated with them, in particular in Photorhabdus and Xenorhabdus. Often the primary obstacle to fully exploiting the potential of Photorhabdus and Xenorhabdus, the partners say, is an inability to identify all of the three elements (BGC, chemical structure and bioactivity).
This collaboration brings together the DGIMI laboratory’s knowledge regarding the molecular genomics and genetics of the bacteria strains Photorhabdus and Xenorhabdus and Nosopharm’s experience in the production of specialised bioactive metabolites from the same strains. The chemical libraries may also be made available to companies and third-party research institutes in connection with screening campaigns for molecules of pharmaceutical and biotechnological interest.
Of the 63 therapeutic products approved by the FDA in 2021, 36 were small molecules. As a result, biopharmaceutical laboratories are keen to discover small bioactive molecules to add to their portfolio of products under development, Nosopharm says.
The collaboration, which began when Nosopharm was founded in 2009, has resulted in the discovery of three antimicrobial classes, for which three patent requests were filed. The patent for the Odilorhabdins class was granted in Europe, the United States, Japan and China.
“We are delighted to be collaborating with the DGIMI laboratory and its teams. This partnership will allow us to bolster our unique expertise in the pharmacological exploitation of the bacteria strains Photorhabdus and Xenorhabdus, which are used exclusively by Nosopharm. Our objective is to discover innovative anti-infective molecules with new modes of action in order to offer solutions in the ongoing fight against antibiotic resistance,” said Philippe Villain-Guillot, co-founder and CEO of Nosopharm.
“As a result of this collaboration, we will be able to fully exploit our original collection of microorganisms in order to facilitate the discovery of new anti-infective molecules, all against the backdrop of a global rise in antibiotic-resistance-related deaths. We will also be able to conduct some fundamental research into the role of these molecules in our tripartite interaction model, consisting of bacteria, nematodes and insects,” said Alain Givaudan, director of research at the DGIMI laboratory.
“The discovery of new molecules and their biological activity is crucial to understanding the interactions, both between microorganisms and between microorganisms and their hosts. This topic is a core component of our curriculum here at the University of Montpellier; this collaboration with Nosopharm will enable constructive interactions between the biotech industry and our pool of students. The exploitation of new natural molecule resources found in our environment seems likely to reveal its true potential in connection with the growing problem of antibiotic resistance, which will be a challenge for future generations,” added Alyssa Carré-Mlouka, senior lecturer at the University of Montpellier and associate of the DGIMI laboratory.
