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Enzybiotics: Enzyme-Based Antibacterials as Therapeutics

  • Dorien Dams
  • Yves BriersEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1148)

Abstract

Antibiotics have saved millions of lives. However, the overuse and misuse of antibiotics have contributed to a rapid emergence of antibiotic resistance worldwide. In addition, there is an unprecedented void in the development of new antibiotic classes by the pharmaceutical industry since the first introduction of antibiotics. This antibiotic crisis underscores the urgent and increasing necessity of new, innovative antibiotics. Enzybiotics are such a promising class of antibiotics. They are derived from endolysins, bacteriophage-encoded enzymes that degrade the bacterial cell wall of the infected cell at the end of the lytic replication cycle. Enzybiotics are featured by a rapid and unique mode-of-action, a high specificity to kill pathogens, a low probability for bacterial resistance development and a proteinaceous nature. (Engineered) endolysins have been demonstrated to be effective in a variety of animal models to combat both Gram-positive and Gram-negative bacteria and have entered different phases of preclinical and clinical trials. In addition, mycobacteriophage-encoded endolysins have been successfully used to inhibit mycobacteria in vitro. In this chapter we focus on the (pre)clinical progress of enzybiotics as potent therapeutic agent against human pathogenic bacteria.

Keywords

Endolysin Enzybiotics Clinical trials Animal models Multidrug-resistance 

Abbreviations

AG

Arabinogalactan

Art

Artilysin

AMP

Antimicrobial peptide

CBD

Cell wall binding domain

CM

Cytoplasmic membrane

CoNS

Coagulase-negative staphylococci

DAP

Daptomycin

EAD

Enzymatically active domain

EDTA

Ethylenediaminetetraacetic acid

GlcNAc

N-acetylglucosamine

GLP

Good laboratory practice

HHP

High hydrostatic pressure

LAL

Limulus amoebocyte lysate

LPS

Lipopolysaccharide

MA

Mycolic acids

MIC

Minimal inhibitory concentration

MRSA

Methicillin-resistant Staphylococcus aureus

MSSA

Methicillin-sensitive Staphylococcus aureus

MurNAc

N-acetylmuramic acid

NA

Not applicable

ND

Not defined

OM

Outer membrane

OMP

Outer membrane permeabilizing

PAE

Post-antibiotic effect

PA-SME

Post-antibiotic sub-MIC effect

PG

Peptidoglycan

SME

Sub-MIC effect

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Laboratory of Applied Biotechnology, Department of BiotechnologyGhent UniversityGhentBelgium

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