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Biofilm disruption: combination of phages with other agents

 

A biofilm is a structured community of bacteria attached to a living or inert surface, embedded in an extracellular polymer matrix, and bound by a protective polymer membrane. Biofilms can form on the surfaces of both human tissue and implanted medical devices, causing chronic infections that are difficult to treat. Current antiseptics and antimicrobials have limited ability to completely eliminate biofilms. However, bacteriophages and some of their enzymes have the ability to disrupt biofilms. In a review published in the journal Nanotechnology, Science and Applications, the authors discuss the potential of using phages and phage enzymes to disrupt biofilms and completely kill the bacteria that form them.

The authors of the review note that phage therapy alone cannot always completely destroy the biofilm and the bacteria that formed it. The most effective approach, in their opinion, is combination therapy with bacteriophages and/or their enzymes and other antimicrobial agents, in particular: antibiotics, antimatrix agents (DNase or dispersin B enzymes, divalent cation chelator, etc.); quorum sensing inhibitors of bacteria in biofilm (curcumin, quercetin, halogenated furanose derivatives, ginseng and garlic extracts, antimicrobial peptides pyrocoricin or microcin B); metal nanoparticles (silver, gold, titanium, copper or zinc), nanoparticles; physical methods (cleaning and rinsing); disinfectants (acid and alkaline disinfectants, ethanol, chlorine dioxide, hydrogen peroxide); monoclonal antibodies; antimicrobial photodynamic therapy, etc.

In vitro models have shown that the synergistic action of monophage preparations, phage cocktails, or phage enzymes with antimicrobial agents ensures successful treatment of biofilm-associated infections. Specifically, this has been demonstrated for biofilms formed by various strains of Pseudomonas aeruginosa , MRSA, Escherichia coli, Enterococcus faecalis, Klebsiells spp, and others. Phages have been used in combination with antibiotics (ciprofloxacin, vancomycin, gentamicin, amikacin, etc.), silver nanoparticles, copper (II) ions, chloride compounds, EDTA, saturated long-chain fatty acids, and even honey.

An important issue is the order in which the phage preparation is administered alongside other antimicrobial agents. Several studies suggest that phage administration should precede other antimicrobial agents.

The review's authors note that the combinations tested in vitro can be tested in clinical practice to prevent or eliminate biofilms on medical devices and on the surface of the human body. However, they emphasize that not all strategies can be considered for combating biofilms inside the human body.

A more detailed description of the trials of combinations of bacteriophages with various biofilm-destroying agents, as well as a list of references to original studies, can be found in the review:

Amankwah S, Abdella K, Kassa T. Bacterial Biofilm Destruction: A Focused Review On The Recent Use of Phage-Based Strategies With Other Antibiofilm Agents. Nanotechnol Sci Appl. 2021, 14: 161-177. https://doi.org/10.2147/NSA.S325594