Aspergillomarasmine, a promising adjuvant to overcome antibiotic resistance

Bacterial resistance to antibiotics poses a significant public health challenge. One mechanism by which bacteria acquire resistance is the synthesis of beta-lactamases that inhibit the activity of beta-lactam antibiotics. Metallo-beta-lactamases (MBL) are a class of these enzymes for which there are currently no clinically available inhibitors to restore the efficacy of beta-lactam antibiotics. Aspergillomarasmine A (AMA), a fungal metabolite, has emerged as a compelling candidate, selectively chelating Zn²⁺ to inactivate MBLs and restore β-lactam activity. This review integrates current knowledge gathered from electronic databases, including ScienceDirect, PubMed, Scopus, Web of Science, and Google Scholar, on the mechanism of action and potential role of AMA in antibiotic/adjuvant co-therapy. Evidence to date suggests that AMA’s unique mode of action may limit the development of rapid resistance, although its clinical efficacy remains unproven. Accelerating AMA’s preclinical and clinical evaluation is imperative to translate its promise role into a novel strategy against multidrug-resistant bacteria.