2D-MoS2‑Based β‑Lactamase Inhibitor for Combination Therapy against Drug-Resistant Bacteria

Despite the remarkable improvement in modern medicine, the ever-increasing abundance of antibiotic-resistant microorganisms remains a catastrophic threat to global health care. β-Lactamase is playing one of the major roles in antibiotic resistance by making the conventional antibacterial agents abortive by destroying their lactam ring. The combination therapy of traditional antibiotics along with β-lactamase inhibitors is a potential solution to this problem. In this work, we have screened various functionalized two-dimensional molybdenum disulfide (2D-MoS2) nanomaterials as enzyme inhibitors that effectively bind with β-lactamase enzyme and reveal competitive inhibition. Among these, carboxylate-functionalized negatively charged 2D-MoS2 is the most potent inhibitor, and in vitro combinatorial application of this with conventional antibiotics has been able to remarkably suppress relevant drug-resistant bacterial growth rate. This study will help to further explore different surface-functionalized 2D nanomaterials with improved β-lactamase inhibition to fight against multidrug-resistant bacterial infections.