Mechanistic insight of lysozyme transport through the outer bacteria membrane with dendronized silver nanoparticles for peptidoglycan degradation

Drug resistance has become a global problem, prompting the entire scientific world to seek alternative methods of dealing with resistant pathogens. Among the many alternatives to antibiotics, two appear to be the most promising: membrane permeabilizers and enzymes that destroy bacterial cell walls. Therefore, in this study, we provide insight into the mechanism of lysozyme transport strategies using two types of carbosilane dendronized silver nanoparticles (DendAgNPs), non-polyethylene glycol (PEG)-modified (DendAgNPs) and PEGylated (PEG-DendAgNPs), for outer membrane permeabilization and peptidoglycan degradation. Remarkably, studies have shown that DendAgNPs can build up on the surface of a bacterial cell, destroying the outer membrane, and thereby allowing lysozymes to penetrate inside the bacteria and destroy the cell wall. PEG-DendAgNPs, on the other hand, have a completely different mechanism of action. PEG chains containing a complex lysozyme resulted in bacterial aggregation and an increase in the local enzyme concentration near the bacterial membrane, thereby inhibiting bacterial growth. This is due to the accumulation of the enzyme in one place on the surface of the bacteria and penetration into it through slight damage of the membrane due to interactions of NPs with the membrane. The results of this study will help propel more effective antimicrobial protein nanocarriers.