# Engineering ArtE2, a polycationic peptide-fused Bacillus endolysin, expands antibacterial activity to Escherichia coli while retaining potency against Staphylococcus aureus

“Engineering ArtE2, a polycationic peptide-fused Bacillus endolysin, expands antibacterial activity to Escherichia coli while retaining potency against Staphylococcus aureus” (2026), by Roxana Portieles et al. Immunology and Microbiology research paper. Original abstract below, unchanged. A free PDF is available.

- Authors: Roxana Portieles, Xinmin Ma, Jianjian Hu, Yuxiu Xu, Hongli Xu, Wang Ling, Xiangyou Gao, Nayanci Portal-González, Rabia Durrani, Ramón Santos et al.
- Published: November 5, 2026
- Field: Immunology and Microbiology
- DOI: https://doi.org/10.21203/rs.3.rs-10886723/v1
- Free PDF: https://www.researchsquare.com/article/rs-10886723/latest.pdf

## Abstract

Background The outer membrane of Gram-negative bacteria restricts access of most exogenously applied endolysins to peptidoglycan. This study aimed to engineer ArtE2 from Bacillus altitudinis Endolysin-2 (E2) by fusing the polycationic decapeptide MKRKKRKKRK to the N-terminus and introducing the substitutions H176Y and T178R, and to evaluate its antibacterial activity against Escherichia coli while determining whether activity against Staphylococcus aureus was retained. Results ArtE2 was obtained as a soluble, highly cationic protein. Molecular docking predicted interactions with several peptidoglycan fragments, including the NAG–NAM dimer. ArtE2 displayed concentration- and time-dependent antibacterial activity against both E. coli ATCC 25922 and S. aureus ATCC 25923, whereas native E2 showed little activity against E. coli. Measurable residual activity was retained across the temperature and pH ranges examined. Molecular dynamics simulations revealed condition-dependent differences in RMSD, with comparatively low values under selected conditions, including pH 7 in the presence of CaCl₂. Conclusions ArtE2 showed enhanced antibacterial activity relative to native E2 against the strains tested. Evaluation against a broader and more clinically diverse bacterial panel is warranted.

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