Zeolitic Imidazolate Framework-8 Triggers the Inhibition of Arginine Biosynthesis to Combat Methicillin-Resistant Staphylococcus Aureus.

Abstract

The self-preservation and intelligent survival abilities of methicillin-resistant Staphylococcus aureus (MRSA) result in the ineffective treatment of many antibiotics. Nano-drug delivery systems have emerged as a new strategy to overcome MRSA infection. ZIF-8 nanoparticles (ZIF-8 NPs) exhibit good antibacterial activities, while its molecular mechanisms are largely elusive. In this study, the ZIF-8 NPs are prepared using the room temperature solution reaction method. The values of minimum inhibitory concentration of ZIF-8 NPs against Escherichia coli and MRSA isolates are 25 and 12.5µg mL-1 , respectively. Transcriptome and metabonomic analyses reveal that ZIF-8 NPs could trigger the inhibition of arginine biosynthesis pathway and the production of ROS, which lead to dysfunctional tricarboxylic acid cycle and disruption of cell membrane integrity, eventually killing MRSA isolates. Moreover, ZIF-8 NPs show desirable treatment and repair effects on mice model of MRSA isolates wound infected-model. The results, for the first time, reveal that the inhibition of arginine biosynthesis mediates the production of ROS and energy metabolism dysfunction contributes to the antibacterial ability of ZIF-8 NPs against MRSA. This study offers a new insight into ZIF-8 NPs combating MRSA isolates.