RESUMEN
Herpes simplex virus type 1 (HSV-1) is a common pathogen that infects 50-90% of the world's population and causes a variety of diseases, some of which can be life-threatening. Silver nanoparticles (AgNPs) have been shown to have broad-spectrum antiviral activity. In this study, we investigated the activity of AgNPs against HSV-1 and found that AgNPs effectively inhibited plaque formation and HSV-1 progeny production, reduced the genomic load, and interfered with HSV-1 mRNA expression and protein synthesis. Transmission electron microscopy showed that AgNPs interacted with HSV-1 and altered the shape of the viral particles. Furthermore, AgNPs affected the entry of HSV-1 into cells as well as their release and cell-to-cell spread. AgNPs were also found to downregulate the expression of pro-inflammatory cytokines upon HSV-1 infection. Combined treatment with AgNPs and acyclovir (ACV) confirmed that AgNPs significantly enhanced the inhibitory effect of ACV against HSV-1. Our findings may contribute to an understanding of the mechanism of the antiviral effect of AgNPs against HSV-1 and help to provide a theoretical basis for their clinical application.
Asunto(s)
Herpes Simple , Herpesvirus Humano 1 , Nanopartículas del Metal , Aciclovir/farmacología , Antivirales/farmacología , Antivirales/uso terapéutico , Herpes Simple/tratamiento farmacológico , Herpesvirus Humano 2 , Humanos , Plata/farmacología , Plata/uso terapéuticoRESUMEN
Pseudomonas aeruginosa is a gram-negative bacterium that exists in various ecosystems, causing severe infections in patients with AIDS or cystic fibrosis. P. aeruginosa can form biofilm on a variety of surfaces, whereby the bacteria produce defensive substances and enhance antibiotic-resistance, making themselves more adaptable to hostile environments. P. aeruginosa resistance represents one of the main causes of infection-related morbidity and mortality at a global level. Iron is required for the growth of P. aeruginosa biofilm. This review summarises how the iron metabolism contributes to develop biofilm, and more importantly, it may provide some references for the clinic to achieve novel anti-biofilm therapeutics by targeting iron activities.
Asunto(s)
Biopelículas/efectos de los fármacos , Hierro/metabolismo , Pseudomonas aeruginosa/fisiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Antibacterianos/farmacología , Fibrosis Quística/complicaciones , Farmacorresistencia Bacteriana , Humanos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificaciónRESUMEN
The decline of clinically effective antibiotics has made it necessary to develop more effective antimicrobial agents, especially for refractory biofilm-related infections. Silver nanoparticles (AgNPs) are a new type of antimicrobial agent that can eradicate biofilms and reduce bacterial resistance, but its anti-biofilm mechanism has not been elucidated. In this study, we investigated the molecular mechanism of AgNPs against multidrug-resistant Pseudomonas aeruginosa by means of anti-biofilm tests, scanning electron microscopy (SEM), and tandem mass tag (TMT)-labeled quantitative proteomics. The results of anti-biofilm tests demonstrated that AgNPs inhibited the formation of P. aeruginosa biofilm and disrupted its preformed biofilm. SEM showed that when exposed to AgNPs, the structure of the P. aeruginosa biofilm was destroyed, along with significant reduction of its biomass. TMT-labeled quantitative proteomic analysis revealed that AgNPs could defeat the P. aeruginosa biofilm in multiple ways by inhibiting its adhesion and motility, stimulating strong oxidative stress response, destroying iron homeostasis, blocking aerobic and anaerobic respiration, and affecting quorum sensing systems. Our findings offer a new insight into clarifying the mechanism of AgNPs against biofilms, thus providing a theoretical basis for its clinical application.
Asunto(s)
Nanopartículas del Metal , Pseudomonas aeruginosa , Antibacterianos/farmacología , Biopelículas , Pruebas de Sensibilidad Microbiana , Proteómica , Plata/farmacologíaRESUMEN
BACKGROUND: The threat of drug-resistant Pseudomonas aeruginosa requires great efforts to develop highly effective and safe bactericide. OBJECTIVE: This study aimed to investigate the antibacterial activity and mechanism of silver nanoparticles (AgNPs) against multidrug-resistant P. aeruginosa. METHODS: The antimicrobial effect of AgNPs on clinical isolates of resistant P. aeruginosa was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). In multidrug-resistant P. aeruginosa, the alterations of morphology and structure were observed by the transmission electron microscopy (TEM); the differentially expressed proteins were analyzed by quantitative proteomics; the production of reactive oxygen species (ROS) was assayed by H2DCF-DA staining; the activity of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) was chemically measured and the apoptosis-like effect was determined by flow cytometry. RESULTS: Antimicrobial tests revealed that AgNPs had highly bactericidal effect on the drug-resistant or multidrug-resistant P. aeruginosa with the MIC range of 1.406-5.625 µg/mL and the MBC range of 2.813-5.625 µg/mL. TEM showed that AgNPs could enter the multidrug-resistant bacteria and impair their morphology and structure. The proteomics quantified that, in the AgNP-treated bacteria, the levels of SOD, CAT, and POD, such as alkyl hydroperoxide reductase and organic hydroperoxide resistance protein, were obviously high, as well as the significant upregulation of low oxygen regulatory oxidases, including cbb3-type cytochrome c oxidase subunit P2, N2, and O2. Further results confirmed the excessive production of ROS. The antioxidants, reduced glutathione and ascorbic acid, partially antagonized the antibacterial action of AgNPs. The apoptosis-like rate of AgNP-treated bacteria was remarkably higher than that of the untreated bacteria (P<0.01). CONCLUSION: This study proved that AgNPs could play antimicrobial roles on the multidrug-resistant P. aeruginosa in a concentration- and time-dependent manner. The main mechanism involves the disequilibrium of oxidation and antioxidation processes and the failure to eliminate the excessive ROS.