Zinc Imidazole Framework-8 Nanoparticles Disperse MRSA Biofilm by Inhibiting Arginine Biosynthesis and Down-Regulating Adhesion-Related Proteins

Nanomaterials, including ZIF-8 nanoparticles (NPs), are shown to be effective antimicrobial agents against Methicillin-resistant Staphylococcus aureus(MRSA). However, the antibiofilm properties and mechanisms of ZIF-8 NPs remain uncertain. In this study, ZIF-8 NPs are prepared using the room temperature solution reaction method and characterized. Biofilm formation inhibition test and biofilm eradication test are performed and the results show that ZIF-8 NPs can inhibit the formation of MRSA biofilm as well as disperse established MRSA biofilm. Proteomics and real-time fluorescence quantitative polymerase chain reaction (PCR) are conducted to prove that ZIF-8 NPs reduce the expression of adhesion-related proteins, namely the fibronectin-binding proteins A and B (fnbA/fnbB), fibrinogen binding protein caking factors A and B (clfA/clfB), elastin binding protein (ebps), and fibrin binding protein (eno). ZIF-8 NPs also inhibit the arginine biosynthesis pathway by affecting the activities of argininosuccinate lyase, ornithine carbamyl transferase, Glutamate dehydrogenase, carbamate kinase, and arginine deiminase. A conclusion can be drawn from the above results that ZIF-8 NPs can inhibit bacterial adhesion and kill bacteria directly, ultimately destroying MRSA biofilm. This study provides a molecular basis for the treatment of MRSA biofilm with ZIF-8 NPs. ZIF-8 NPs, as an independent antibiofilm agent, inhibits the formation of MRSA biofilm and eradicates the established MRSA biofilm by down-regulating the arginine biosynthesis and adhesion protein synthesis related genes, inducing the accumulation of ROS (reactive oxygen species) to cause the death of bacterial individuals while inhibiting bacterial adhesion to prevent biofilm formation. image