Science

Antimicrobial resistance

At Nosopharm our mission is to discover and develop first-in-class therapies to treat infectious diseases, especially in the context of antimicrobial resistance.

Infectious diseases are a major cause of global mortality, leading to more than 8 million deaths in 2019, before the Covid-19 pandemic crisis. In 2019 an estimated 4.95 million deaths were associated with bacterial antimicrobial resistance. The increase in antimicrobial resistance, making infections much harder to treat, represents a critical challenge for global health.

In this context, Nosopharm aims to contribute to the fight against infectious diseases, especially antimicrobial resistance, by discovering novel anti-infective therapies. Our R&D programs are based on our unique expertise in the exploitation of the bacteria Photorhabdus and Xenorhabdus.

Nosopharm’s drug discovery platform is based on these two underexplored antimicrobial-producing bacteria. Nosopharm is the only biotech company to explore the bacteria Photorhabdus and Xenorhabdus for anti-infective applications.

Photorhabdus & xenorhabdus

Photorhabdus and Xenorhabdus are the essential symbiotic of the entomopathogenic nematodes Heterorhabditis and Steinernema. They are present all over the world, existing in a large variety of ecosystems.

They have a fascinating and very uncommon lifecycle. The lifecycle requires that Photorhabdus and Xenorhabdus produce a high diversity of small molecules to interact with their host nematodes, their target insects, their microbiota counterparts, and with their microbial competitors and predators. This feature is supported by the high content of PKS and NRPS genes in their genomes. These bioactive molecules are naturally designed to be non-toxic to the eukaryotic nematode and to diffuse within the biological matrices of insects. These properties act as primary filters for drugability and make their chemical scaffolds very promising starting points for drug-likeness.

These unique qualities mean that the exploitation of Photorhabdus and Xenorhabdus is a very elegant strategy to discover novel innovative therapeutics for human and animal health.

Nosopharm's drug discovery platform

Nosopharm has been developing and improving its proprietary, unique drug discovery platform for more than a decade.

This platform exploits the bacteria Photorhabdus and Xenorhabdus to identify novel and more efficient bioactive molecules. It capitalizes on our unique experience in the exploration of the specialized bioactive metabolism of these bacteria.

Nosopharm’s drug discovery platform stands on 3 pillars :

 

Proprietary techniques to stimulate the micro-organisms to produce their specialized bioactive metabolites under artificial lab conditions

Specific know-how in the fermentation of Photorhabdus and Xenorhabdus to produce selected bioactive molecules in the 10-100 mg scale

Ever-expanding proprietary databases enabling a faster identification of the yet undescribed bioactive molecules of Photorhabdus and Xenorhabdus.

We are working with industrial and academic partners to offer our innovative platform for their collaborative drug discovery programs.

To explore our partnering opportunities, contact us 

Publications

Lanois-Nouri A, Pantel L, Fu J, Houard J, Ogier JC, Polikanov YS, Racine E, Wang H, Gaudriault S, Givaudan A, Gualtieri M

The Odilorhabdin Antibiotic Biosynthetic Cluster and Acetyltransferase Self-Resistance Locus Are Niche and Species Specific [https://journals.asm.org/doi/10.1128/mbio.02826-21]

mBio (2022)

Pantel L, Juarez P, Serri M, Boucinha L, Lessoud E, Lanois A, Givaudan A, Racine EGualtieri M

Missense Mutations in the CrrB Protein Mediate Odilorhabdin Derivative Resistance in Klebsiella pneumoniae [https://journals.asm.org/doi/10.1128/AAC.00139-21]

Antimicrob Agents Chemother (2021)

Loza E, Sarciaux M, Ikaunieks M, Katkevics M, Kukosha T, Trufilkina N, Ryabova V, Shubin K, Pantel L Serri M, Huseby DL, Cao S, Yadav K, Hjort K, Hughes D, Gualtieri M, Suna E, Racine E

Structure-activity relationship studies on the inhibition of the bacterial translation of novel Odilorhabdins analogues [https://www.sciencedirect.com/science/article/abs/pii/S0968089620302832]

Bioorg Med Chem (2020)

Racine E, Gualtieri M

From Worms to Drug Candidate: The Story of Odilorhabdins, a New Class of Antimicrobial Agents [https://www.frontiersin.org/articles/10.3389/fmicb.2019.02893/full]

Front Microbiol (2019)

Sarciaux M, Pantel L , Midrier C, Serri M, Gerber C, Marcia de Figueiredo R, Campagne JM, Villain-Guillot P, Gualtieri M, Racine E

Total Synthesis and Structure–Activity Relationships Study of Odilorhabdins, a New Class of Peptides Showing Potent Antibacterial Activity [https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00790]

J Med Chem (2018)

Racine E, Nordmann P, Pantel L, Sarciaux M, Serri M, Houard J, Villain-Guillot P, Demords A, Vingsbo Lundberg C, Gualtieri M

In Vitro and In Vivo Characterization of NOSO-502, a Novel Inhibitor of Bacterial Translation [https://journals.asm.org/doi/full/10.1128/AAC.01016-18]

Antimicrob Agents Chemother (2018)

Pantel L, Florin T, Dobosz-Bartoszek M, Racine E, Sarciaux M, Serri M, Houard J, Campagne JM, de Figueiredo RM, Midrier C, Gaudriault S, Givaudan A, Lanois A, Forst S, Aumelas A, Cotteaux-Lautard C, Bolla JM, Vingsbo Lundberg C, Huseby DL, Hughes D, Villain-Guillot P, Mankin AS, Polikanov YS, Gualtieri M

Odilorhabdins, Antibacterial Agents that Cause Miscoding by Binding at a New Ribosomal Site [https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30182-5]

Mol Cell (2018)

Gualtieri M, Ogier JC, Pagès S, Givaudan A, Gaudriault S

Draft Genome Sequence and Annotation of the Entomopathogenic Bacterium Xenorhabdus szentirmaii Strain DSM16338 [https://journals.asm.org/doi/10.1128/genomeA.00190-14]

Genome Announc (2014)

Houard J, Aumelas A, Noël T, Pages S, Givaudan A, Fitton-Ouhabi V, Villain-Guillot PGualtieri M

Cabanillasin, a new antifungal metabolite, produced by entomopathogenic Xenorhabdus cabanillasii JM26 [https://www.nature.com/articles/ja201358]

J Antibiot (2013)

In Vivo Pharmacodynamic Characterization of a Novel Odilorhabdin Antibiotic, NOSO-502, against Escherichia coli and Klebsiella pneumoniae in a Murine Thigh Infection Model https://journals.asm.org/doi/10.1128/AAC.01067-18

Antimicrobial Agents and Chemotherapy (2018)