Narrow spectrum antibiotics Our research aims to develop innovative antibacterial strategies that are both highly effective and respectful of the host microbiota. We are designing pathogen-specific prodrugs. These compounds are selectively activated by broad-spectrum β-lactamases produced by Gram-negative priority pathogens identified by the WHO. This project, coordinated by our team and financed by the PIA-AMR, brings together eight complementary teams from Université Paris Cité, PSL, Institut Pasteur, CEA, and CNRS, combining expertise in chemical synthesis, structural biology, biochemistry, metagenomics, and host–pathogen interactions.

Novel therapies against Mycobacterium abscessus. Mycobacterium abscessus has emerged as a major opportunistic pathogen causing chronic lung infections in cystic fibrosis patients. These infections are extremely difficult to treat due to intrinsic multidrug resistance, with eradication rates dropping to ~25% in macrolide-resistant cases. We have demonstrated that a triple combination therapy-two β-lactams (penam and carbapenem classes) combined with a second-generation diazabicyclooctane (DBO) β-lactamase inhibitor-displays strong synergistic activity in vitro, in infected macrophages, and in a murine model. We now aim to optimize this therapeutic strategy by identifying its molecular targets and, in the longer term, by developing carbapenems and DBO derivatives specifically tailored to this pathogen.

Associated publications:

• Burke K, Herail Q, Zerguine I, Bougault C, Arthur M, Etheve-Quelquejeu M, Iannazzo L. (2025). Optimization of Prodrug Activation by Enzymatic Cleavage of the β-lactam Ring of Carbapenems. Chemistry, Aug 18;31(46):e01534

• Razew A, Herail Q, Miyachiro M, Anoyatis-Pelé C, Bougault C, Dessen A, Arthur M, Simorre JP. (2024). Monitoring Drug-Protein Interactions in the Bacterial Periplasm by Solution Nuclear Magnetic Resonance Spectroscopy. J Am Chem Soc, Apr 3;146(13):9252-9260.

• Le Moigne V, Bitar M, Arthur M, Mainardi J-L, Herrmann J-L. The addition of amoxicillin improves the efficacy of the imipenem-avibactam combination against Mycobacterium abscessus in a mouse model of infection. (2025). Antimicrob Agents Chemother. 2025 Aug 6;69(8):e0053425.

• Bitar M, Le Moigne V, Herrmann JL, Arthur M, Mainardi JL. In vitro, intracellular and in vivo synergy between amoxicillin, imipenem and relebactam against Mycobacterium abscessus. (2025). J Antimicrob Chemother. 2025 Jun 3;80(6):1560-1567.

• Sanchez L, Bitar M, Herail Q, Dorchêne D, Hugonnet JE, Arthur M, Mainardi JL. (2024). In vitro and intracellular activity of vaborbactam combined with β-lactams against Mycobacterium abscessus. J Antimicrob Chemother. Aug 1;79(8):1914-1918.