Host-Defense-Peptide-Mimickingβ-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-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.

Recent trends and developments in the asymmetric synthesis of profens

The profens belong to a class of nonsteroidal anti-inflammatory drugs(NSAIDs),which exert significant antiinflammatory,analgesic,antipyretic and other pharmacological effects.A considerable number of catalytic asymmetric strategies for the synthesis of enantioenriched profens have been introduced.Herein are outlined recent trends and developments of promising catalytic enantioselective systems for the generation of profens and their derivatives.According to the reaction type,we divided these transformations into three categories:Transition metal-catalyzed asymmetric hydrogenations,transition metal-catalyzed asymmetric cross-couplings and organocatalytic asymmetric transformations.Overviews of generic reaction mechanisms are presented.Ideally,this tutorial review will motivate further interest in the catalytic asymmetric synthesis of highly enantioenriched profens.

Ultrasmall Ga-ICG nanoparticles based gallium ion/photodynamic synergistic therapy to eradicate biofilms and against drug-resistant bacterial liver abscess

Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics.Here,we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles(ICG-Ga NPs)containing clinically approved gallium(Ⅲ)(Ga^(3+))and liver targeting indocyanine green(ICG)molecules to eradicate multi-drug resistant(MDR)bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking.The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane,further boost the endocytosis of Ga^(3+),then replace iron in bacteria cells to disrupt bacterial iron metabolism,and demonstrate the synergetic bacterial killing and biofilm disrupting effects.The ICG-Ga NPs show an excellent therapeutic effect against extended spectrumβ-lactamases Escherichia coli(ESBL E.coli)and significantly improve treatment outcomes in infected liver abscess and keratitis.Meanwhile,the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route,guaranteeing the biocompatibility.The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.