Bacteriophage-Derived Depolymerases against Bacterial Biofilm

Abstract

In addition to specific antibiotic resistance, the formation of bacterial biofilm causes another level of complications in attempts to eradicate pathogenic or harmful bacteria, including difficult penetration of drugs through biofilm structures to bacterial cells, impairment of immunological response of the host, and accumulation of various bioactive compounds (enzymes and others) affecting host physiology and changing local pH values, which further influence various biological functions. In this review article, we provide an overview on the formation of bacterial biofilm and its properties, and then we focus on the possible use of phage-derived depolymerases to combat bacterial cells included in this complex structure. On the basis of the literature review, we conclude that, although these bacteriophage-encoded enzymes may be effective in destroying specific compounds involved in the formation of biofilm, they are rarely sufficient to eradicate all bacterial cells. Nevertheless, a combined therapy, employing depolymerases together with antibiotics and/or other antibacterial agents or factors, may provide an effective approach to treat infections caused by bacteria able to form biofilms.

Temperate Bacteriophages—The Powerful Indirect Modulators of Eukaryotic Cells and Immune Functions

“…Biofilm formation has a great impact on bacterial physiology and survival, allowing cells to resist various deleterious environmental factors [60]. Biofilm is of great importance in the pathogenicity of many bacteria, including P. aeruginosa, making it extremely difficult to fight these bacteria [61].…”

Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter Baumannii

“…Overall, the depolymerase treatment were unable to completely inhibit or remove biofiolms and the number of viable bacterial counts in the biofilms were similar to the untreated controls [18][19][20]25], with a few exceptions [24,29]. These suggested that using depolymerases as a stand-alone treatment might not be sufficient in controlling infections associated with biofilms.…”

“…In addition, depolymerases also present high specificity toward a narrow range of target polysaccharides (specific capsular type of the bacteria). In some cases, depolymerases might only be active against a subset of bacteria of their parent phage which are already specific to a small set of bacteria strains [18,29,36]. Such narrow host spectrum would greatly limit the wider therapeutic application of depolymerases.…”

“…Instead, they disintegrate the CPS of bacteria to make them susceptible to host immune attack and antibacterial treatment [15]. Recombinant depolymerases have been shown to protect mice from fatal systemic bacterial infection [16,17] and to disrupt biofilms for enhanced antimicrobial activity [18][19][20][21][22].…”

Phage Digestion of a Bacterial Capsule Imparts Resistance to Two Antibiotic Agents

“…The tail fiber (TF) with function of capsular depolymerase is another attractive virion protein. Some applications of phage-derived depolymerase have been used in penetration of bacterial cell wall, reducing impairment of immunological response, or against bacterial biofilm [22,23]. Furthermore, depolymerase therapy as an antibiotic was shown to be in robust health of mice study [24].…”