ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Synthetic antimicrobial peptide LD4-PP protects the host against E. coli-induced cell death
Provisionally accepted
Soumitra Mohanty1,2
John Kerr White1,2Yundi Yin1,2Taj Muhammad3
Isak Demirel4Adam A. Strömstedt3Sunithi Gunasekera3Natalia Ferraz3Ulf Göransson3
Annelie Brauner1,2*- 1Karolinska Institutet, Stockholm, Sweden
- 2Karolinska Universitetssjukhuset, Stockholm, Sweden
- 3Uppsala Universitet, Uppsala, Sweden
- 4Orebro universitet, Örebro, Sweden
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With antibiotic resistance being a major global concern, there is a huge need of new treatment options to fight bacterial infections. In this study, we highlight the antibacterial and host-protective roles of a novel synthetic antimicrobial peptide in uropathogenic Escherichia coli infected uroepithelial cells. This peptide, designed from a fragment of human cathelicidin LL-37 and named LD4-PP, was found to be highly potent against clinical isolates of E. coli, as well as ESBL-producing and multi-drug resistant E. coli. Additionally, LD4-PP inhibited the formation of new biofilm, damaged both the bacterial surface and the bacterial genome. LD4-PP also modulated the host cell lipid vacuole, caveolin-1 and Rho GTPase B affecting bacterial survival. Furthermore, LD4-PP exerts immunomodulatory effects by modulating free radical formation, expression of antioxidants and inflammasome-mediated cell death. Pronounced uroepithelial cell death was observed after E. coli infection which was significantly inhibited by LD4-PP without affecting the cellular toxicity. Overall, the peptide LD4-PP is shown to be a strong candidate for future clinical applications, particularly to prevent and treat urinary tract infections.
Keywords: E. coli, Synthetic antimicrobial peptide, immune response, Urinary tract infection, innate immunity
Received: 15 Sep 2025; Accepted: 06 Nov 2025.
Copyright: © 2025 Mohanty, White, Yin, Muhammad, Demirel, Strömstedt, Gunasekera, Ferraz, Göransson and Brauner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Annelie Brauner, annelie.brauner@ki.se
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