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Published on: December 9, 2022
Cationic Antimicrobial Carbon Acid Polymer Eradicates Pseudomonas aeruginosa and Staphylococcus aureus Biofilms
Wenbin Zhong1,2, Lin Ruan1, Chongyun Tan1
1Centre for Antimicrobial Bioengineering, Nanyang Technological University, Singapore 637459, Singapore.
Abstract:
Biofilm-associated infections exhibit high tolerance to antibiotics and antimicrobials, posing a significant challenge to wound management. Pseudomonas aeruginosa and Staphylococcus aureus are among the most prevalent pathogens in biofilm-associated wound infections. Here, we report a main-chain cationic antimicrobial polymer, poly(butylimidazolium) (PIM1), whose imidazolium units feature an acidic C2-H carbon center. PIM1 demonstrated potent broad-spectrum activity against multidrug-resistant (MDR) bacteria with minimal cytotoxicity toward multiple mammalian cell lines in vitro. PIM1 retained fast bactericidal activity under physiological conditions, including whole blood and high bacterial inoculum. Interestingly, its potency increased 2- to 4-fold in the presence of serum. PIM1 also eliminated antibiotic-tolerant persister cells and eradicated biofilms formed by MDR pathogens. In vivo, 7-day continuous topical administration of PIM1 on murine wounds caused no observable toxicity. In murine excisional wound infection models, topical PIM1 treatment achieved >99% eradication of P. aeruginosa and S. aureus biofilms, outperforming imipenem and vancomycin controls, respectively. These findings support PIM1 as a safe and effective therapeutic candidate for treating biofilm-associated wound infections caused by MDR bacteria.
Insights
A new antimicrobial polymer, poly(butylimidazolium) (PIM1), effectively eradicates biofilms from multidrug-resistant bacteria in wound infections. PIM1 shows broad-spectrum activity and minimal toxicity, offering a promising therapeutic candidate.
Area of Science:
- Antimicrobial polymers
- Wound infection treatment
- Biofilm eradication
Background:
- Biofilm-associated infections are difficult to treat due to high antimicrobial tolerance.
- Pseudomonas aeruginosa and Staphylococcus aureus are key pathogens in wound infections.
- Current treatments face challenges with multidrug-resistant (MDR) bacteria.
Purpose of the Study:
- To develop and evaluate a novel main-chain cationic antimicrobial polymer, poly(butylimidazolium) (PIM1).
- To assess PIM1's efficacy against MDR bacteria and biofilms in wound infections.
- To determine PIM1's safety and therapeutic potential in vivo.
Main Methods:
- Synthesis and characterization of poly(butylimidazolium) (PIM1).
- In vitro testing of PIM1 against MDR bacteria, persister cells, and biofilms.
- In vivo efficacy and toxicity studies in murine wound infection models.
Main Results:
- PIM1 exhibited broad-spectrum bactericidal activity with low cytotoxicity.
- PIM1 demonstrated potent activity under physiological conditions, including serum presence.
- PIM1 eradicated established biofilms and persister cells in vitro.
- Topical PIM1 treatment in murine models achieved >99% eradication of P. aeruginosa and S. aureus biofilms.
- No observable toxicity was noted with continuous topical PIM1 administration.
Conclusions:
- PIM1 is a potent antimicrobial agent effective against MDR bacteria and biofilms.
- PIM1 demonstrates safety and efficacy for treating biofilm-associated wound infections.
- PIM1 represents a promising therapeutic candidate for challenging wound infections.
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