Bacteriophages and Biofilm
Biofilms are an extremely common adaptation that allows bacteria to colonize hostile environments. They present unique challenges for antibiotics and biocides, due both to the nature of the extracellular matrix and the presence of metabolically inactive persistent cells within the biofilm. Such chemicals can be highly effective against planktonic bacterial cells while remaining essentially ineffective against biofilms. In contrast, bacteriophages appear to have a greater ability to combat this widespread form of bacterial growth. The high density of bacteria in biofilms facilitates the action of bacteriophages by enabling rapid and efficient host infection and subsequent amplification of the bacteriophage. Bacteriophages also possess a range of properties that make biofilms susceptible to their action. They are known to produce (or can induce) enzymes that degrade the extracellular matrix. They are also capable of infecting persistent cells that remain dormant within them but are reactivated when they become metabolically active. Some cultured biofilms also appear better able to support bacteriophage replication than comparable planktonic systems. It is perhaps not surprising that bacteriophages, as natural predators of bacteria, possess the ability to combat this common form of bacterial life.
In early studies demonstrating the potential of bacteriophages for biofilm control, Hanlon et al. [24] found that Pseudomonas aeruginosa bacteriophages could destroy bacteria in a mature (20-day-old) biofilm and (perhaps surprisingly given their size) could even diffuse through the thickest (12%) alginate gel studied, although diffusion was slower than through thinner alginate gels. Hanlon also observed that the bacteriophages studied could directly degrade the alginate polymer, apparently via a bacteriophage-borne enzymatic activity, although this was not identified. Regardless of the activity, it differed significantly from the highly restricted tail spike proteins.
Sillankorva et al. utilized bacteriophages from both Pseudomonas fluorescens and Staphylococcus lentus, demonstrating the effective reduction of single-species and mixed biofilms using these agents. Both bacteriophages were fully sequenced, and it was shown that neither encoded a polysaccharide depolymerase (although the Pseudomonas fluorescens bacteriophage encoded an endopeptidase). Similarly, Doolittle et al. [25] showed that the Escherichia coli T4 bacteriophage spreads efficiently through a biofilm, even though it encodes no other polysaccharide depolymerases except for a very restricted tail spike protein that is only released from the bacteriophage tail during host cell penetration. However, Doolittle et al. [25] also worked with the Pseudomonas aeruginosa bacteriophage E79 and showed that it was less effective at penetrating biofilms than T4.
While it is clear that naturally occurring bacteriophages can penetrate biofilms even when they do not produce polysaccharide depolymerases (or when these have a very limited function), not all studies have shown efficient infection within biofilms, and some researchers continue to believe that EPS-degrading enzymes are necessary for biofilm applications.
Tait et al. reported that a mixture of three bacteriophages could completely eliminate a single-species biofilm, but that this was less effective when other, insensitive bacterial species were present. Kay et al. [27] also showed that mixed biofilms can diminish the effectiveness of bacteriophages. Nevertheless, Sillankorva et al. [1] demonstrated that efficiency in model biofilms can be high even when a bacteriophage targets a single bacterial species, stating that „phages can be adopted as a method for killing a specific bacterium even when its host lives in a mixed consortium.“ Sillankorva et al. [1] also showed that mature (seven-day-old) biofilms can be effectively controlled using bacteriophages.
It is therefore clear that natural bacteriophages can and often do express enzymes capable of disrupting biofilms, but that these do not appear to be essential for infectivity in this situation. The potential for the induction of such enzymes from the host genome is, of course, much more difficult to identify.
Bacteriophages possess unique properties and show great promise in the control of biofilms. However, such applications are still evolving, and large-scale applications are still under development. Therefore, the identification of the most effective approaches must currently remain speculative. Over time, and as more results are published, best practices for such applications will naturally emerge.
Translation of the source:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790368/
Bacteriophages and Biofilms
David R. Harper, Helena M. R. T. Parracho, James Walker, Richard Sharp, Gavin Hughes, Maria Werthén, Susan Lehman, and Sandra Morales1
