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Bactericidal Activity of Non-Cytotoxic Cationic Nanoparticles against Clinically and Environmentally Relevant
Anna Maria Schito1, Gabriella Piatti1, Debora Caviglia1
1Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, I-16132 Genova, Italy.
Abstract:
Difficult-to-treat bacterial infections caused by resistant human and plant pathogens severely afflict hospitals, and concern the agri-food sectors. Bacteria from the Pseudomonadaceae family, such as P. aeruginosa, P. putida, P. fluorescens, and P. straminea, can be responsible for severe nosocomial infections in humans. P. fragi is the major cause of dairy and meat spoilage, while P. syringae can infect a wide range of economically important plant species, including tobacco, kiwi, and tomato. Therefore, a cationic water-soluble lysine dendrimer (G5-PDK) was tested on several species of Pseudomonas genus. Interestingly, G5-PDK demonstrated variable minimum inhibitory concentrations (MICs), depending on their pigment production, on Pseudomonas aeruginosa (1.6-> 6.4 µM), MICs = 3.2-6.4 µM on P. putida clinical isolates producing pyoverdine, and very low MICs (0.2-1.6 µM) on strains that produced non-pigmented colonies. Time-kill experiments established the rapid bactericidal activity of G5-PDK. In the cytotoxicity experiments on human keratinocytes, after 4 h of treatment with G5-PDK at concentrations 16-500 × MIC, more than 80% of viable cells were observed, and after 24 h, the selectivity indices were maintained above the maximum value reported as acceptable. Due to its proven bactericidal potency and low cytotoxicity, G5-PDK should be seriously considered to counteract clinically and environmentally relevant Pseudomonas isolates.
Insights
A novel lysine dendrimer, G5-PDK, shows potent bactericidal activity against problematic Pseudomonas species, including human and plant pathogens. This compound exhibits low cytotoxicity, making it a promising agent for combating resistant bacterial infections.
Area of Science:
- Microbiology
- Biotechnology
- Materials Science
Background:
- Resistant bacterial infections caused by the Pseudomonadaceae family pose significant threats to human health and agriculture.
- Species like *P. aeruginosa* cause nosocomial infections, while others like *P. syringae* damage crops, and *P. fragi* spoils food.
Purpose of the Study:
- To evaluate the efficacy of a cationic water-soluble lysine dendrimer, G5-PDK, against various *Pseudomonas* species.
- To assess the bactericidal activity and cytotoxicity of G5-PDK.
Main Methods:
- Minimum inhibitory concentrations (MICs) were determined for different *Pseudomonas* strains.
- Time-kill experiments were conducted to assess bactericidal kinetics.
- Cytotoxicity assays were performed on human keratinocytes.
Main Results:
- G5-PDK demonstrated variable MICs against *P. aeruginosa*, with lower concentrations effective against non-pigmented strains.
- Rapid bactericidal activity was confirmed through time-kill experiments.
- G5-PDK showed low cytotoxicity to human keratinocytes, maintaining high selectivity indices.
Conclusions:
- G5-PDK exhibits significant bactericidal potency against clinically and environmentally relevant *Pseudomonas* isolates.
- Its low cytotoxicity suggests a favorable safety profile for potential therapeutic applications.
- G5-PDK represents a promising candidate for developing new strategies against resistant bacterial infections.
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