Bacteriophage-Mediated Control of Biofilm: A Promising New Dawn for the Future

Abstract

Biofilms are complex microbial microcolonies consisting of planktonic and dormant bacteria bound to a surface. The bacterial cells within the biofilm are embedded within the extracellular polymeric substance (EPS) consisting mainly of exopolysaccharides, secreted proteins, lipids, and extracellular DNA. This structural matrix poses a major challenge against common treatment options due to its extensive antibiotic-resistant properties. Because biofilms are so recalcitrant to antibiotics, they pose a unique challenge to patients in a nosocomial setting, mainly linked to lower respiratory, urinary tract, and surgical wound infections as well as the medical devices used during treatment. Another unique property of biofilm is its ability to adhere to both biological and man-made surfaces, allowing growth on human tissues and organs, hospital tools, and medical devices, etc. Based on prior understanding of bacteriophage structure, mechanisms, and its effects on bacteria eradication, leading research has been conducted on the effects of phages and its individual proteins on biofilm and its role in overall biofilm removal while also revealing the obstacles this form of treatment currently have. The expansion in the phage host-species range is one that urges for improvement and is the focus for future studies. This review aims to demonstrate the advantages and challenges of bacteriophage and its components on biofilm removal, as well as potential usage of phage cocktail, combination therapy, and genetically modified phages in a clinical setting.

Keywords: bacteriophages; biofilms; depolymerase; endolysin; phage therapy.

FIGURE 1

Comparing the structural mechanism of ancient Chinese military tactics and bacterial biofilm.

FIGURE 2

Overview of the biofilm formation process. (1) Surface sensing operated by surface swarming. (2) Attachment stage involving the initial reversible attachment and the subsequent irreversible attachment. (3) Excretion of EPS that signifies the creation of biofilm. (4) Maturation of biofilm that involves quorum sensing to facilitate collective behavioral adjustments to surrounding changes. (5) Dispersal of biofilm structure following the release of planktonic bacteria initiating biofilm formation elsewhere.

FIGURE 3

Depiction of biofilm removal using phages and its derived enzymes. (1). Bacteriophage therapy, consisting of single phage therapy and cocktail therapy, that is used for intra- to extracellular degradation of the bacterial structure. (2). Phage-derived endolysin used for extra- to intracellular degradation of the bacterial structure. (3). Phage-derived depolymerase, presented as free enzyme or tail spike protein, that is used for chemical dispersion of the biofilm matrix. (4). Combination therapy using both phages and other antimicrobial compounds, such as antibiotics. (5). Genetically-modified phages that enlarge the host-species interaction range.