Potential for Bacteriophage Endolysins to Supplement or Replace Antibiotics in Food Production and Clinical Care
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Michael J Love1, Dinesh Bhandari2,3, Renwick C J Dobson4,5
1Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury, Christchurch 8041, New Zealand. michael.love@pg.canterbury.ac.nz.
Abstract:
There is growing concern about the emergence of bacterial strains showing resistance to all classes of antibiotics commonly used in human medicine. Despite the broad range of available antibiotics, bacterial resistance has been identified for every antimicrobial drug developed to date. Alarmingly, there is also an increasing prevalence of multidrug-resistant bacterial strains, rendering some patients effectively untreatable. Therefore, there is an urgent need to develop alternatives to conventional antibiotics for use in the treatment of both humans and food-producing animals. Bacteriophage-encoded lytic enzymes (endolysins), which degrade the cell wall of the bacterial host to release progeny virions, are potential alternatives to antibiotics. Preliminary studies show that endolysins can disrupt the cell wall when applied exogenously, though this has so far proven more effective in Gram-positive bacteria compared with Gram-negative bacteria. Their potential for development is furthered by the prospect of bioengineering, and aided by the modular domain structure of many endolysins, which separates the binding and catalytic activities into distinct subunits. These subunits can be rearranged to create novel, chimeric enzymes with optimized functionality. Furthermore, there is evidence that the development of resistance to these enzymes may be more difficult compared with conventional antibiotics due to their targeting of highly conserved bonds.
Insights
Bacterial resistance to antibiotics is a growing problem. Bacteriophage endolysins offer a promising alternative, potentially overcoming resistance due to their unique mechanism and bioengineering potential.
Area of Science:
- Microbiology
- Biotechnology
- Drug Discovery
Background:
- Antibiotic resistance is a significant global health threat, with multidrug-resistant bacteria rendering treatments ineffective.
- Conventional antibiotics face challenges due to widespread bacterial resistance, necessitating novel therapeutic strategies.
- Bacteriophage-encoded lytic enzymes (endolysins) are emerging as potential alternatives to antibiotics.
Purpose of the Study:
- To explore the potential of bacteriophage endolysins as alternatives to conventional antibiotics.
- To investigate the efficacy and limitations of endolysins, particularly in Gram-negative bacteria.
- To highlight the prospects of bioengineering endolysins for enhanced therapeutic applications.
Main Methods:
- Review of preliminary studies on exogenous endolysin application.
- Analysis of endolysin efficacy in Gram-positive versus Gram-negative bacteria.
- Examination of endolysin modular structure for bioengineering possibilities.
Main Results:
- Endolysins show promise in disrupting bacterial cell walls, with greater efficacy observed in Gram-positive bacteria.
- The modular structure of endolysins allows for bioengineering of chimeric enzymes with optimized functions.
- Bacterial resistance to endolysins may be less likely compared to conventional antibiotics due to targeting conserved bonds.
Conclusions:
- Bacteriophage endolysins represent a viable alternative to antibiotics for combating bacterial infections in humans and animals.
- Bioengineering offers a pathway to enhance endolysin functionality and broaden their therapeutic spectrum.
- Targeting conserved bonds suggests endolysins may circumvent existing resistance mechanisms.
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