A systematic review of the use of bacteriophages for in vitro biofilm control

Abstract

Bacteriophages (phages) are very promising biological agents for the prevention and control of bacterial biofilms. However, little is known about the parameters that can influence the efficacy of phages on biofilms. This systematic review provides a summary and analysis of the published data about the use of phages to control pre-formed biofilms in vitro, suggesting recommendations for future experiments in this area. A total of 68 articles, containing data on 605 experiments addressing the efficacy of phages to control biofilms in vitro were included, after a search conducted in Web of Science, Embase, and Medline (PubMed). The data collected from each experiment included information about biofilm growth conditions, phage characteristics, treatment conditions and biofilm reduction. In most cases, biofilms were formed in the surface of microtiter plates (82.5%); the median time for biofilm formation was 24 h, as is the median treatment duration. Quantification of biofilm biomass (52.6%), viable cells (25.5%) and metabolic activity (17.9%) were the most common biofilm assessment methods. Correlation analysis revealed that some phage parameters can influence the treatment outcome: higher phage concentrations were strongly associated with improved biofilm control, leading to higher levels of biofilm reduction, and phages with higher burst sizes and shorter latent periods seem to be the best candidates to control biofilms in vitro. However, the great variability of the methodologies used prompts the need for the development of standardized in vitro methodologies to characterize phage/biofilm interactions and to assess the efficacy of phages to control biofilms.

Exploiting phage-antibiotic synergies to disrupt Pseudomonas aeruginosa PAO1 biofilms in the context of orthopedic infections

“…A limitation of this technique, however, is that the added dye accumulates and is not re-metabolized, meaning that a decrease in metabolic activity will not be detectable once a plateau is reached. It therefore still needs to be combined with the evaluation of biomass, and CFU residual counts for a global picture of treatment effects on biofilms ( 85 ).…”

How Do Phages Disrupt the Structure of Enterococcus faecalis Biofilm?

“…In summary, phages can disrupt preformed biofilms in several ways: by enzymatic degradation, cell lysis, and interfering with bacterial communication systems, such as quorum sensing. Understanding how phages interact with preformed biofilms is crucial for the development of phage-based therapies [18][19][20].…”

Efficacy and Experience of Bacteriophages in Biofilm-Related Infections

“…Moreover, bacteriophages can infect stationary-phase cells and eliminate them upon reactivation. Bacteriophages also have the ability to produce enzymes inhibiting quorum sensing activity and biofilm production [10,15].…”

“…Several studies have analyzed the antibiofilm activity of single phages in vitro. Variables such as smaller phage genomes, higher burst sizes, shorter phage latent periods, or higher phage concentrations are frequently associated with greater biofilm reduction [15]. The most commonly studied multidrug-resistant bacteria involved in nosocomial infections have been examined.…”