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A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
Poly(hexamethylene guanidine): An Effective Compound in Tackling Persistent Bacterial Subpopulations
Weilin Liu1, Jiang Zhang2, Liang Chen1
1College of Bioengineering, Beijing Polytechnic University, Beijing 100176, China.
Abstract:
Persistent bacteria (PB) are a subpopulation of dormant cells that tolerate high antibiotic concentrations and cause chronic, hard-to-treat infections, posing a serious global health threat. In this study, the antibacterial efficacy of six cationic polymers, poly(hexamethylene guanidine) (PHMG), polyethyleneimines of different molecular weights, α-polylysine, ε-polylysine, and polyacrylamide, against persistent bacteria was systematically evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of these cationic polymers against susceptible and persistent methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Escherichia coli (E. coli) were determined using a microbroth dilution method, while cytotoxicity to mouse fibroblast (L929) cells was assessed via MTT assay. PHMG demonstrated superior antibacterial activity, with MBC values as low as 2 μg/mL against persistent MSSA, markedly outperforming the other polymers tested. The key novelties of this work are (i) the first establishment of a cationic polymer library with diverse structural parameters for persistent bacteria clearance, offering a potential strategy for treating recalcitrant infections; and (ii) the elucidation of quantitative correlations between polymer charge density and hydrophobic chain segments with antimicrobial efficacy through structure-activity relationship analysis, providing a theoretical basis for the rational design of anti-persistent materials.
Insights
Poly(hexamethylene guanidine) (PHMG) shows strong antibacterial effects against persistent bacteria, which cause difficult-to-treat infections. This study provides a new library of cationic polymers for combating these resilient bacterial populations.
Area of Science:
- Microbiology
- Polymer Science
- Infectious Diseases
Background:
- Persistent bacteria (PB) are dormant cells that tolerate antibiotics, causing chronic infections and posing a global health threat.
- Developing novel strategies to eliminate PB is crucial for treating recalcitrant infections.
Purpose of the Study:
- To evaluate the antibacterial efficacy of six cationic polymers against persistent bacteria.
- To establish structure-activity relationships for designing effective anti-persistent materials.
Main Methods:
- Systematic evaluation of six cationic polymers against persistent methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Escherichia coli (E. coli).
- Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using microbroth dilution.
- Cytotoxicity assessment against mouse fibroblast (L929) cells via MTT assay.
Main Results:
- Poly(hexamethylene guanidine) (PHMG) exhibited superior antibacterial activity, with MBC values as low as 2 μg/mL against persistent MSSA.
- Other tested cationic polymers showed less efficacy compared to PHMG.
- Structure-activity relationship analysis revealed correlations between polymer charge density, hydrophobic segments, and antimicrobial efficacy.
Conclusions:
- PHMG is a highly effective agent against persistent bacteria.
- This study presents the first library of cationic polymers for targeting persistent bacteria, offering potential strategies for recalcitrant infections.
- Quantitative structure-activity relationships provide a basis for rational design of novel anti-persistent materials.
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