Polyethyleneimine Capped Silver Nanoclusters as Efficient Antibacterial Agents.
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ABSTRACT:
SUBMITTER: Xu D
PROVIDER: S-EPMC4808997 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Since its discovery nearly a century ago, antibiotics has been one of the most effective methods in treating infectious diseases and limiting pathogen spread. However, pathogens often build up antibiotic resistance over time, leading to serious failure of the treatment. Silver nanoparticle (AgNP) is an appealing alternative, but successful treatment of the bacterial infection requires a plentiful supply of AgNP, which can negatively impact human health if people are excessively exposed to the particles. Here, we present a method to overcome this challenge by synthesizing nanodiamond-supported AgNP noncovalently conjugated with albumin molecules to achieve enhanced antibacterial activity and strengthened biocompatibility. Using Escherichia coli as a model bacterium, we found that the albumin-conjugated silver-diamond nanohybrids showed a long-term bactericidal effect after 36 days of the treatment at the AgNP concentration of 250?µg?mL-1. Moreover, the toxicity of the nanohybrids to human cells (including human fibroblasts, lung adenocarcinoma epithelial cells, and breast adenocarcinoma cells) is low even at the particle concentration of 500?µg?mL-1. The method provides a general and practical solution to the concerns of bacterial resistance against AgNP and issues associated with the size, shape, aggregation, and toxicity of AgNP are largely resolved. Finally, we demonstrate that the nanohybrids can be readily incorporated into natural polysaccharides (such as guar gum) to form three-in-one hydrogels, showing promising applications in nanomedicine.
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Project description:Antibacterial therapy is of paramount importance in treatment of several acute and chronic infectious diseases caused by pathogens. Over the years extensive use and misuse of antimicrobial agents has led to emergence of multidrug resistant (MDR) and extensive drug resistant (XDR) pathogens. This drastic escalation in resistant phenotype has limited the efficacy of available therapeutic options. Thus, the need of the hour is to look for alternative therapeutic approaches to mitigate healthcare concerns caused due to MDR bacterial infections. Nanoparticles have gathered much attention as potential candidates for antibacterial therapy. Equipped with advantages of, wide spectrum bactericidal activity at very low dosage, inhibitor of biofilm formation and ease of permeability, nanoparticles have been considered as leading therapeutic candidates to curtail infections resulting from MDR bacteria. However, substrate non-specificity of efflux pumps, particularly those belonging to resistance nodulation division super family, have been reported to reduce efficacy of many potent antibacterial therapeutic drugs. Previously, we had reported antibacterial activity of polysaccharide-capped silver nanoparticles (AgNPs) toward MDR bacteria. We showed that AgNPs inhibits biofilm formation and alters expression of cytoskeletal proteins FtsZ and FtsA, with minimal cytotoxicity toward mammalian cells. In the present study, we report no reduction in antibacterial efficacy of silver nanoparticles in presence of AcrAB-TolC efflux pump proteins. Antibacterial tests were performed according to CLSI macrobroth dilution method, which revealed that both silver nanoparticles exhibited bactericidal activity at very low concentrations. Further, immunoblotting results indicated that both the nanoparticles modulate the transporter AcrB protein expression. However, expression of the membrane fusion protein AcrA did show a significant increase after exposure to AgNPs. Our results indicate that both silver nanoparticles are effective in eliminating MDR Enterobacter cloacae isolates and their action was not inhibited by AcrAB-TolC efflux protein expression. As such, the above nanoparticles have strong potential to be used as effective and alternate therapeutic candidates to combat MDR gram-negative Enterobacterial pathogens.
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Project description:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to various antibacterial agents, we performed transcriptomics on MTB bacilli exposed to several test compounds as well as known drugs (capreomycin, cycloserine, ethionamide, isoniazid, kanamycin, moxifloxacin, PA-824, rifampicin, streptomycin). Bacteria were exposed for 16 hrs to various concentrations of each drug (different multiples of the compound's MIC), as noted in the title of each sample. RNA was isolated and applied to arrays provided by TIGR under the NIAID contract N01-AI-15447
2015-11-11 | E-GEOD-71200 | biostudies-arrayexpress