Magnetic Nanoparticle Clusters with Remarkable Antibacterial Activity

By Benedette Cuffari, M.Sc.Aug 11 2017

Biofilms consists of a collective group of microorganisms that attach to each other or to a surface such as bacteria and the extracellular matrix secreted by the organisms¹. A variety of pathogenic and problematic microorganisms may take shelter in these biofilms which are difficult to eradicate due to the inability of antimicrobial agents to penetrate the biofilm.

Biofilms in water distribution and storage systems can cause significant public health concerns due to the various pathogenic bacteria they house, as well as increase the economic costs of maintaining these systems as these biofilms also cause corrosion of pipes and other metal substrates they attach to^1,2. Researchers from the Rice University’s Department of Civil and Environmental Engineering in collaboration with the University of Science and Technology of China’s Department of Chemistry have recently discovered that magnetic nanoparticle clusters – conjugated with polyvalent phages could enhance the biofilm penetration thereby suppressing the bacterial growth².

Pedro J. J. Alvarez’s team utilized bacteriophages, which are the viruses that infect and multiply in bacteria, to effectively kill bacteria that usually resist chemical disinfection. Polyvalent phages that can attack multiple strains of bacteria were combined with nanoclusters that are modified with the coating of an amino group facilitating the attachment of bacteriophages’ head to the nanoclusters thereby leaving the infectious tails accessible to infect the bacterial biofilms². This group of Researchers used a relatively weak magnetic field (660 gauss) to allow the phages bound to nanoclusters to adhere to the biofilm and destroy them².

The Iron oxide (Fe₃O₄) colloidal nanocrystals (CNCs) were synthesize by a solvothermal reaction, which were then treated with tetraethyl orthosilicate (TEOS) to produce core shell Fe₃O₄-SiO₂ CNCs³. Amino groups are then introduced onto the surface of Fe₃O₄-SiO₂ CNCs by reacting with a modifying agent (3-aminopropyl) triethyl siloxane (APTES) and ammonium hydroxide (NH₄OH) to form Fe₃O₄-SiO₂-NH2 core shell CNCs. The Fe₃O₄-SiO₂-NH2 core shell CNCs were further used to synthesize Fe₃O₄-SiO₂-COOH core shell CNCs and the chitosan-coated Fe₃O₄ (CS- Fe₃O₄) CNCs²

Polyvalent phage PEL1 belonging to the Podoviridae family was immobilized and conjugated onto the Fe₃O₄ (CS- Fe₃O₄) CNCs in such a way that the CNCs are attached to the bacteriophages’ heads by a covalent bonding by forming amide linkages to form phage loaded magnetic nanocrystals (PEL1- CS- Fe₃O₄) ². Because of this, the Researchers achieved a phage loading of (5.2 ± 0.7) × 10³ centers of infection per 1 μg of chitosan-coated CNCs (CS-Fe₃O₄). Two strains of bacteria, Escherichia coli (C3000) and Pseudomonas aeruginosa (PA01) were used to test the plaque formation capabilities of chitosan-coated CNCs (CS-Fe₃O₄) ².

The results showed that the plaque formation, which is measured as the area of petri dish infection, in case of both the bacterial strains was 99.1% in the phage loaded magnetic colloidal nanocrystals (PEL1- CS- Fe₃O₄) as compared to the 3.2% in the CNCs that were functionalized with the carboxyl groups (Fe₃O₄-SiO₂-COOH) ². Furthermore, the PEL1- CS- Fe₃O₄ was found to remove 88.7 ± 2.8% of the biofilm coverage area after 6 hours of treatment in the newly established biofilms formed from these two species on a glass surface².

Even though the bacteria could develop resistance, the Authors believe that the ability of the phage enhanced CNCs to destroy the bacteria relatively quickly would make it relatively difficult^2,3. The research team led by Pedro J. J. Alvarez is now working to develop phage “cocktails” that could combine different types of bacteriophages that can destroy several strains of bacteria while also incorporating antibiotics to prevent resistance.

This research puts forward a novel conjugation approach that combines the fields of nanotechnology and virology to destroy bacterial biofilms that are difficult to penetrate using antimicrobial agents. Due to the ability of these magnetic CNCs to penetrate the biofilms and destroy more than one strains of bacteria, this method could be especially useful in disinfecting water distribution and storage system.

The use of this conjugation approach could be extended to other applications of phages for microbial control by providing access to relatively inaccessible locations within the biofilms².

Image Credit:

musmellow/ Shutterstock.com

References:

1. “Biofilms” – Nature.com
2. “Enhanced biofilm penetration for microbial control by polyvcalent phages conjugated with magnetic colloidal nanoparticle clusters (CNCs)” L. Li, P. Yu, et al. Environmental Science: Nano. (2017). DOI: 10.1039/c7en00414A.

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