In vitro and in vivo antimicrobial activity of combined therapy of silver nanoparticles and visible blue light against Pseudomonas aeruginosa

Abstract

Silver nanoparticles (AgNPs) have been used as potential antimicrobial agents against resistant pathogens. We investigated the possible therapeutic use of AgNPs in combination with visible blue light against a multidrug resistant clinical isolate of Pseudomonas aeruginosa in vitro and in vivo. The antibacterial activity of AgNPs against P. aeruginosa (1×10 5 colony forming unit/mL) was investigated at its minimal inhibitory concentration (MIC) and sub-MIC, alone and in combination with blue light at 460 nm and 250 mW for 2 hours. The effect of this combined therapy on the treated bacteria was then visualized using transmission electron microscope. The therapy was also assessed in the prevention of biofilm formation by P. aeruginosa on AgNP-impregnated gelatin biopolymer discs. Further, in vivo investigations were performed to evaluate the efficacy of the combined therapy to prevent burn-wound colonization and sepsis in mice and, finally, to treat a real infected horse with antibiotic-unresponsive chronic wound. The antimicrobial activity of AgNPs and visible blue light was significantly enhanced ( P <0.001) when both agents were combined compared to each agent alone when AgNPs were tested at MIC, 1/2, or 1/4 MIC. Transmission electron microscope showed significant damage to the cells that were treated with the combined therapy compared to other cells that received either the AgNPs or blue light. In addition, the combined treatment significantly ( P <0.001) inhibited biofilm formation by P. aeruginosa on gelatin discs compared to each agent individually. Finally, the combined therapy effectively treated a horse suffering from a chronic wound caused by mixed infection, where signs of improvement were observed after 1 week, and the wound completely healed after 4 weeks. To our knowledge, this combinatorial therapy has not been investigated before. It was proved efficient and promising in managing infections caused by multidrug resistant bacteria and could be used as an alternative to conventional antibiotic therapy.

Antimicrobial blue light inactivation of pathogenic microbes: State of the art

“…In a similar study from the same group, Nour El Din et al investigated the therapeutic application of aBL in combination with AgNPs against P. aeruginosa (Nour El Din et al, 2016). The antimicrobial activity of AgNPs and aBL at 460 nm (250 mW/cm 2 for 1 h) was significantly enhanced when both agents were combined compared to each agent alone when AgNPs were tested at MIC, 1/2, or 1/4 MIC.…”

Early Stages of Antibacterial Damage of Metallic Nanoparticles by TEM and STEM-HAADF

“…structure as the overall shape becomes irregular and the cell wall is distorted after direct contact. Metallic NPs and other ionic species that they might release from their surface when in solution could interact with the anionic lipopolysaccharides of Gram-negative cell wall, as it has been reported before [ 33 , 34 ]. These interactions then, lead to the disequilibrium on the cell causing permeation and resulting finally in cell death [ 35 , 36 ].…”

Effect of Flavonoid-Coated Gold Nanoparticles on Bacterial Colonization in Mice Organs

“…Besides, plasma proteins and plasma components can also interact with the NPs surface, and this can affect their biodistribution [ 26 , 27 , 28 ], cellular uptake, and bioactivity [ 29 , 30 , 31 ]. Recently, a few in vivo studies have been carried out that include combined therapy of silver NPs, and visible blue light against Pseudomonas [ 32 ], quercetin loaded PLGA for Escherichia coli [ 33 ], and tridecaptin-antibiotic conjugates against Klebsiella pneumoniae [ 34 ].…”