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,...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-peptidemimickingβ-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.Theβ-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,theβ-peptide polymer also showed excellent therapeutic effect Escherichia coli pyogenic liver abscess.Together,we believed that theβ-peptide polymer had a feasible clinical potential to treat bacterial infection diseases.展开更多
基金This work was supported by the National Natural Science Foundation of China(nos.81971667,22075078,and 21861162010)the National Natural Science Foundation of China for Innovative Research Groups(no.51621002)+1 种基金the Key Research and Development Project of Zhejiang Province(no.2020C03035)the Fundamental Research Funds for the Zhejiang Provincial Universities,China(no.2021XZZX034).
文摘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-peptidemimickingβ-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.Theβ-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,theβ-peptide polymer also showed excellent therapeutic effect Escherichia coli pyogenic liver abscess.Together,we believed that theβ-peptide polymer had a feasible clinical potential to treat bacterial infection diseases.
