A Promising Strategy against Multidrug-Resistant Pseudomonas aeruginosa.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA), a World Health Organization high-priority pathogen,represents a major clinical threat due to limited treatment options. Its intrinsic resistance is driven in part by extremely low outer-membrane permeability, which restricts antibiotic uptake, while the increasing prevalence of metallo-β-lactamase (MBL)-producingstrains, particularly NDM-expressing isolates, poses a critical therapeutic challenge, conferring resistance to both carbapenems and cefiderocol, with few effective inhibitors available. In this study, we evaluated the potential of a series of unique biomimeticsiderophore conjugates in combating CRPA. As an initial approach, tris-catecholate siderophore−meropenem conjugates weresynthesized and demonstrated to overcome nonenzymatic carbapenem resistance in P. aeruginosa, including porin loss and effluxupregulation, in an iron-dependent manner. 

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