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.

Highlights

  • Endolysins are gaining importance in recent years due to their broad lytic activities against Gram-positive and Gram-negative bacterial cells [1,2]

  • Endolysins are involved in peptidoglycan degradation during cell lysis, which is regulated by different phage lytic enzymes and holins [4]

  • Within the bacterial host cell at the late stage of phage lytic cycle, holin is produced, which makes a hole in the bacterial cytoplasmic membrane and creates a channel to facilitate lysin delivery to the bacterial peptidoglycan, which results in cleavage of specific peptidoglycan bonds and disrupts the bacterial structure (Figure 4) [4]

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Summary

Introduction

Endolysins are gaining importance in recent years due to their broad lytic activities against Gram-positive and Gram-negative bacterial cells [1,2]. Endolysins are bacteriophageencoded enzymes, which act by hydrolyzing the host cell wall and subsequently allowing the release of bacteriophage progenies. Such enzymes are essential components of the lytic phage life cycle and are a promising alternative to antibiotics [1,2]. The lytic activity of endolysins is classified into different types, namely; (a) acetylmuramidases, (b) transglycosylases, (c) glucosaminidases, (d) amidases, and (e) endopeptidases [1,3] These five different types are further explained in this review to emphasize their mode of action, as well as regulation of expression. It aims to provide information to continue advancing endolysin research It highlights the importance of phage lytic enzymes as an effective alternative against antibiotic-resistant pathogens and discusses their challenges and limitations

History of Endolysins
Endolysin Structure and Mode of Action
Regulation of Expression
Endolysins as Antibacterial Agent
Human Medicine
Agriculture and Plants
Biotechnology
The Effect of Endolysins on the Normal Microbiota
Endolysins and Antibiotics
MGAS5005 prophage
11. Insights into the Clinical Trials of Engineered Endolysins
12. Challenges in Clinical Trials
Findings
13. Conclusions and Future Perspectives
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