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Peer-reviewedCC BY 4.0Frontiers in Microbiology

Engineering endolysins as antibacterial biologics: protein engineering design strategies and trade-offs

  • Susmita Saha
  • Szilvia Barkó
  • Prithwiraj Kirtania
  • Priyanka Bhowmik
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Abstract

Endolysins, the phage murein hydrolases, are promising alternatives to conventional antibiotics. They are highly target specific, rarely induce resistance and spare commensal microbiota. Synergy between endolysins and certain antibiotics has also been well documented, which further supports their therapeutic potential. However, clinical translation is constrained by protein instability, immunogenicity, limited Gram-negative bactericidal activity and short in vivo half-life. This narrative review examines protein engineering strategies for endolysin development and reconciles conflicting mechanistic observations in the literature. It proposes a trade-off framework and context-dependent design principles for engineering next-generation endolysin-based therapeutics.

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Cite

BibTeXRIS
BibTeX
@article{saha2026engineering,
  title = {{Engineering endolysins as antibacterial biologics: protein engineering design strategies and trade-offs}},
  author = {Susmita Saha and Szilvia Barkó and Prithwiraj Kirtania and Priyanka Bhowmik},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = nov,
  doi = {10.3389/fmicb.2026.1944212},
  url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1944212},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Engineering endolysins as antibacterial biologics: protein engineering design strategies and trade-offs
AU  - Susmita Saha
AU  - Szilvia Barkó
AU  - Prithwiraj Kirtania
AU  - Priyanka Bhowmik
PY  - 2026
DA  - 2026/11/06
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.1944212
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1944212
AB  - Endolysins, the phage murein hydrolases, are promising alternatives to conventional antibiotics. They are highly target specific, rarely induce resistance and spare commensal microbiota. Synergy between endolysins and certain antibiotics has also been well documented, which further supports their therapeutic potential. However, clinical translation is constrained by protein instability, immunogenicity, limited Gram-negative bactericidal activity and short in vivo half-life. This narrative review examines protein engineering strategies for endolysin development and reconciles conflicting mechanistic observations in the literature. It proposes a trade-off framework and context-dependent design principles for engineering next-generation endolysin-based therapeutics.
SN  - 1664-302X
ER  -