Assuntos
Fármacos Anti-HIV , Inibidores da Fusão de HIV , Infecções por HIV , Inibidores da Protease de HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Quimioterapia Combinada , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Humanos , Lopinavir/uso terapêutico , Maleimidas , Peptídeos , Ritonavir/uso terapêutico , Carga ViralRESUMO
AIMS: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. METHODS AND RESULTS: The results showed that compound 1 suppressed the expression of QS-related genes and showed the best inhibitory activity to the pqs system of wild-type Ps. aeruginosa PAO1 with an IC50 of 20.22 µmol L-1 . The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration-dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand-binding domain of the Lys-R type transcriptional regulator PqsR as a competitive antagonist. CONCLUSIONS: The quinoline-based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. SIGNIFICANCE AND IMPACT OF STUDY: The study showed that the quinoline-based derivatives could be used as an anti-virulence agent for treating Ps. aeruginosa infections.
Assuntos
Pseudomonas aeruginosa , Piocianina , Antibacterianos/química , Proteínas de Bactérias/metabolismo , Biofilmes , Endopeptidases/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Elastase Pancreática/metabolismo , Pseudomonas aeruginosa/metabolismo , Piocianina/metabolismo , Percepção de Quorum , Tetraciclinas/farmacologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismoRESUMO
Coherent transition radiation in the terahertz (THz) region with energies of sub-mJ/pulse has been demonstrated by relativistic laser-driven electron beams crossing the solid-vacuum boundary. Targets including mass-limited foils and layered metal-plastic targets are used to verify the radiation mechanism and characterize the radiation properties. Observations of THz emissions as a function of target parameters agree well with the formation-zone and diffraction model of transition radiation. Particle-in-cell simulations also well reproduce the observed characteristics of THz emissions. The present THz transition radiation enables not only a potential tabletop brilliant THz source, but also a novel noninvasive diagnostic for fast electron generation and transport in laser-plasma interactions.
