Enhancement of Inhibition Rate of Antibiotic Against Bacteria by Molecularly Imprinted Nanoparticles Targeting Alarmone Nucleotides As Antibiotic Adjuvants.
Journal of materials chemistry B(2022)
摘要
Antibiotic tolerance and resistance in bacteria have caused a great threat to humankind. Bacteria can rapidly accumulate alarmone nucleotides (guanosine tetra- and pentaphosphate, usually denoted as (p)ppGpp) to repair damaged DNA under adverse conditions. The inhibition synthetase enzyme activity of (p)ppGpp, indirectly preventing synthesis, or promoting degradation, has been reported; however, transferring these strategies to practical applications is still a challenging task due to the lack of highly effective molecules for these purposes. Here, an approach based on molecularly imprinted polymer nanoparticles (MIP-NPs) as antibiotic adjuvants was proposed, where MIP-NPs with specific recognition sites were used to capture alarmone nucleotides released by bacteria during stringent response activation. Enhanced inhibition rates of 40-80% were achieved in the presence of the MIP-NPs. The dose of antibiotic could be greatly reduced by utilizing the MIP-NPs as adjuvants for a similar deactivation effectiveness. Good biocompatibility (no obvious hemolysis or cytotoxic effects) and apparent antimicrobial efficiency for resisting wound infection in vivo support the fact that well-designed MIP-NPs have a bright future in dealing with the growing threat of antibiotic tolerance and resistance.
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