Cell Wall-Binding Proteins-Armed Controlled-Release Nanodelivery System Enhances Nisin's Efficacy against...

Area of Science:

• Microbiology
• Nanotechnology
• Drug Delivery

Background:

• Streptococcus pneumoniae causes severe infections, with rising antibiotic resistance challenging current treatments.
• Nisin is an effective antibiotic against S. pneumoniae but lacks stability at physiological pH.
• Innovative delivery systems are needed to improve nisin's therapeutic potential.

Purpose of the Study:

• To develop a nanodelivery system for nisin to enhance its stability and efficacy against S. pneumoniae.
• To exploit the acidic microenvironment of infections for targeted drug release.
• To evaluate the system's effectiveness in a preclinical model of antibiotic-resistant S. pneumoniae pneumonia.

Main Methods:

• Fabrication of a nisin-loading module using oxidized hyaluronic acid and catechol chitosan.
• Functionalization of the module with a S. pneumoniae-specific endolysin cell wall binding domain (CBDcpl-1) for targeted delivery.
• Assessment of nisin release under acidic conditions and in vivo efficacy in a mouse pneumonia model.

Main Results:

• The nanodelivery system demonstrated pH-responsive nisin release, accumulating at infection sites.
• The system significantly improved survival rates in mice with antibiotic-resistant S. pneumoniae pneumonia.
• Reduced bacterial loads were observed in mice treated with the nanodelivery system compared to free nisin.

Conclusions:

• The developed nanodelivery system effectively enhances nisin's stability and targeted delivery.
• This approach shows significant promise for combating antibiotic-resistant S. pneumoniae infections.
• The strategy offers a potential solution for improving the clinical application of peptide antibiotics.