Phage-Encoded Endolysins

Abstract

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

Keywords: antibiotic resistance; bacteriophages; endolysin.

Figure 2

Modular configuration models of common phage endolysins. (a) Model with one N-terminal enzymatically active domain (EAD) and a C-terminal cell wall-binding domain (CBD). (b) Multi-domain model with two EADs and a C-terminal CBD. (c) Multi-domain model with a CBD located between two EADs. (d) Modular endolysin with a C-terminal EAD and an N-terminal CBD. (e) Simple globular model of an EAD with no CBD. (f) Model of a tethered signal-arrest-release (SAR) endolysin localized to the periplasmic membrane before release and activation of lysis function [24].

Figure 1

Timeline showing a brief history of endolysin research work.

Figure 3

Schematic representation of the basic structure of bacterial cell wall peptidoglycan with possible catalytic activities of endolysins indicated. A sub-class of Glycosidases, N-acetyl-β-D-muramidases cleave the β-1,4 bonds between NAM (N-acetylmuramic acid) and NAG (N-acetylglucosamines), and N-acetyl-β-D-glucosidases cleave the β-1,4 bonds between NAG and NAM residues. N-acetylmuramoyl-L-alanine amidases which are amidases cleave the amide bonds between NAM and L-alanine. Endopeptidases cleave interpeptide and stem peptide–interpeptide bridges.

Figure 4

Mechanism of action of endolysin.

Figure 5

The schematic diagram shows the lytic efficacy of bacteriophages and endolysins. (A) Bacterial strains getting resistance against specific phage after phage therapy. (B) Phage endolysin therapy shows better killing efficiency than phage cocktail therapy.

Figure 6

Bacteriophage endolysins as an antibacterial agent. (A) Phage-derived endolysin protects humans, animals, plants that are extremely infected with antibiotic-resistant pathogens and also inhibits the prevalence of antibiotic resistance via other food chains. (B) Overuse of antibiotics in food chains and human and veterinary medicine causes uncontrollable bacterial infections with multidrug resistance that leads to future pandemics.

Figure 7

Biofilm growth stages and degradation: (A) the stages of bacterial biofilm formation from the initial attachment to mature biofilm formation, (B) the process of biofilm dispersal using phage endolysins and phage-derived enzymes as agents of biofilm degradation and bacterial cell lysis.

Figure 8

Relationship of microbiota disturbance with developing diseases in different systems.