Host-Defense-Peptide-Mimicking β-Peptide Polymer Acting as a Dual-Modal Antibacterial Agent by Interfering Quorum Sensing and Killing Individual Bacteria Simultaneously

Host defense peptides (HDPs) are one of the potentially promising agents for infection diseases due to their broad spectrum and low resistance rate, but their clinical applications are limited by proteolytic instability, high-cost, and complicated synthesis process. Here, we report a host-defense-peptide -mimicking beta-peptide polymer that resists proteolysis to have enhanced the activity under physiological conditions, excellent antimicrobial efficiency even at high density of bacteria, and low cost for preparation. The beta-peptide polymer demonstrated quorum sensing (QS) interference and bactericidal effect against both bacterial communities and individual bacterium to simultaneously block bacterial communication and disrupt bacterial membranes. The hierarchical QS network was suppressed, and main QS signaling systems showed considerably down-regulated gene expression, resulting in excellent biofilm eradication and virulence reduction effects. The dual-modal antibacterial ability possessed excellent therapeutic effects in Pseudomonas aeruginosa pneumonia, which could inhibit biofilm formation and exhibit better antibacterial and anti-inflammatory efficiency than clinically used antibiotics, levofloxacin. Furthermore, the beta-peptide polymer also showed excellent therapeutic effect Escherichia coli pyogenic liver abscess. Together, we believed that the beta-peptide polymer had a feasible clinical potential to treat bacterial infection diseases.

Automated summary

In this study, a host-defense-peptide-mimicking beta-peptide polymer was developed as a potential treatment for bacterial infection diseases. The polymer showed resistance to proteolysis, enhanced antimicrobial activity, and low cost for preparation. It also demonstrated quorum sensing interference and bactericidal effects, leading to effective biofilm eradication and virulence reduction. Additionally, the beta-peptide polymer showed therapeutic effects in Pseudomonas aeruginosa pneumonia and Escherichia coli pyogenic liver abscess.