2. Academic Validation
  3. An anti-virulence drug targeting the evolvability protein Mfd protects against infections with antimicrobial resistant ESKAPE pathogens

An anti-virulence drug targeting the evolvability protein Mfd protects against infections with antimicrobial resistant ESKAPE pathogens

  • Nat Commun. 2025 Apr 28;16(1):3324. doi: 10.1038/s41467-025-58282-8.
Seav-Ly Tran # 1,  Lucie Lebreuilly # 1,  Delphine Cormontagne # 1,  Samantha Samson 1 2,  Thu Ba Tô 1 3,  Marie Stosskopf 1,  Rozenn Dervyn 1,  Anne Grießhammer 4 5,  Jacobo de la Cuesta-Zuluaga 4 5,  Lisa Maier 4 5,  Thierry Naas 6,  Simona Mura 3,  Didier Rognan 7,  Julien Nicolas 3,  Gwenaëlle André 2,  Nalini Ramarao 8
Affiliations

Affiliations

  • 1 Université Paris-Saclay, INRAE, Micalis Institute, Jouy-en-Josas, France.
  • 2 Université Paris-Saclay, INRAE, MaIAGE, Jouy-en-Josas, France.
  • 3 Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, France.
  • 4 Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
  • 5 Cluster of Excellence 'Controlling Microbes to Fight Infections', University of Tübingen, Tübingen, Germany.
  • 6 Team ReSIST, INSERM U1184, School of Medicine Université Paris-Saclay, LabEx LERMIT, Assistance Publique/Hôpitaux de Paris, French NRC for Carbapenemase-Producing Enterobacterales. Bicêtre Hospital, Le Kremlin-Bicêtre, France.
  • 7 Université de Strasbourg, CNRS, UMR 7200 LiT, Illkirch, France.
  • 8 Université Paris-Saclay, INRAE, Micalis Institute, Jouy-en-Josas, France. nalini.ramarao@inrae.fr.
  • # Contributed equally.
PMID: 40295486 DOI: 10.1038/s41467-025-58282-8
Abstract

The increasing incidence of Antibiotic resistance and the decline in the discovery of novel Antibiotics have resulted in a global health crisis, particularly, for the treatment of infections caused by Gram-negative bacteria, for which therapeutic dead-ends are alarming. Here, we identify and characterize a molecule, NM102, that displays antimicrobial activity exclusively in the context of Infection. NM102 inhibits the activity of the non-essential Mutation Frequency Decline (Mfd) protein by competing with ATP binding to its active site. Inhibition of Mfd by NM102 sensitizes pathogenic bacteria to the host immune response and blocks infections caused by the clinically-relevant bacteria Klebsiella pneumoniae and Pseudomonas aeruginosa, without inducing host toxicity. Finally, NM102 inhibits the mutation and evolvability function of Mfd, thus reducing the Bacterial capacity to develop antimicrobial resistance. These data provide a potential roadmap for the development of drugs to combat antimicrobial resistance.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-179565
    99.77%, 突变频率下降蛋白抑制剂
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