Gram-negative endolysins: overcoming the outer membrane obstacle

Hazel M Sisson; Simon A Jackson; Robert D Fagerlund; Suzanne L Warring; Peter C Fineran

doi:10.1016/j.mib.2024.102433

Gram-negative endolysins: overcoming the outer membrane obstacle

Curr Opin Microbiol. 2024 Apr:78:102433. doi: 10.1016/j.mib.2024.102433. Epub 2024 Feb 12.

Authors

Hazel M Sisson¹, Simon A Jackson², Robert D Fagerlund², Suzanne L Warring³, Peter C Fineran⁴

Affiliations

¹ Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Bioprotection Aotearoa, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
² Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Bioprotection Aotearoa, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
³ Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
⁴ Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Bioprotection Aotearoa, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, PO Box 56, Dunedin 9054, New Zealand. Electronic address: peter.fineran@otago.ac.nz.

PMID: 38350268
DOI: 10.1016/j.mib.2024.102433

Abstract

Our ability to control the growth of Gram-negative bacterial pathogens is challenged by rising antimicrobial resistance and requires new approaches. Endolysins are phage-derived enzymes that degrade peptidoglycan and therefore offer potential as antimicrobial agents. However, the outer membrane (OM) of Gram-negative bacteria impedes the access of externally applied endolysins to peptidoglycan. This review highlights recent advances in the discovery and characterization of natural endolysins that can breach the OM, as well as chemical and engineering approaches that increase antimicrobial efficacy of endolysins against Gram-negative pathogens.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Infective Agents* / metabolism
Bacteriophages* / metabolism
Endopeptidases / chemistry
Endopeptidases / genetics
Endopeptidases / pharmacology
Gram-Negative Bacteria / metabolism
Peptidoglycan / metabolism

Substances

endolysin
Anti-Bacterial Agents
Peptidoglycan
Endopeptidases
Anti-Infective Agents