Herrera-Espejo Soraya, Bouvier Maxime, Findlay Jacqueline, Pachón Jerónimo, Cisneros José Miguel, Pachón-Ibáñez María Eugenia, Nordmann P
Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital/CSIC/University of Seville, Seville, Spain.
Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
Sci Rep. 2025 Aug 1;15(1):28047. doi: 10.1038/s41598-025-13554-7.
Infection with metallo β-lactamase (MBL)-producing Pseudomonas aeruginosa poses a global health challenge due to its multidrug resistance and the paucity of available antibiotic therapies. Because MBL-producing P. aeruginosa requires zinc ions to hydrolyze β-lactams, it is proposed that meso-dimercaptosuccinic acid (DMSA), a heavy metal chelator, may bind to the zinc ions of the MBL active site necessary for its activity. The bactericidal and synergistic activity of imipenem plus DMSA was studied against the PAO1 reference strain of P. aeruginosa and five isogenic PAO1 strains producing the MBLs NDM-1, IMP-1, IMP-10, IMP-13, and VIM-2. The efficacy of imipenem and DMSA alone or in combination was tested in a murine model of peritoneal sepsis. In vitro, combination with DMSA increased the activity of imipenem against all MBL-producing strains and had a synergistic effect. In a murine peritoneal sepsis model, we found that combination with DMSA improved the efficacy of imipenem for NDM-1- and IMP-producers.
产金属β-内酰胺酶（MBL）的铜绿假单胞菌感染因其多重耐药性以及可用抗生素治疗手段匮乏，对全球健康构成了挑战。由于产MBL的铜绿假单胞菌需要锌离子来水解β-内酰胺，因此有人提出，重金属螯合剂内消旋二巯基琥珀酸（DMSA）可能会与该酶活性所需的MBL活性位点上的锌离子结合。研究了亚胺培南加DMSA对铜绿假单胞菌PAO1参考菌株以及五株产生MBL（NDM-1、IMP-1、IMP-10、IMP-13和VIM-2）的同基因PAO1菌株的杀菌和协同活性。在小鼠腹膜败血症模型中测试了亚胺培南和DMSA单独或联合使用的疗效。在体外，与DMSA联合使用可增强亚胺培南对所有产MBL菌株的活性，并具有协同作用。在小鼠腹膜败血症模型中，我们发现与DMSA联合使用可提高亚胺培南对产NDM-1和IMP菌株的疗效。
