9IO2

Tilapia Piscidin-TP2-5

Summary for 9IO2

• Entry DOI: 10.2210/pdb9io2/pdb
• NMR Information: BMRB: 36683
• Descriptor: LYS-LYS-CYS-ILE-ALA-LYS-ALA-ILE-LEU-LYS-LYS-ALA-LYS-LYS-LEU-LEU-LYS-LYS-LEU-VAL-ASN-PRO (1 entity in total)
• Functional Keywords: structure from cyana 3.98.15, antimicrobial protein
• Biological source: Oreochromis niloticus
• Total number of polymer chains: 1
• Total formula weight: 2486.30

Authors

Huang, Y.P.,Chang, C.F. (deposition date: 2024-07-08, release date: 2025-07-16, Last modification date: 2026-07-29)

Primary citation

Yeh, J.C.,Hazam, P.K.,Lin, Y.Y.,Chang, Y.C.,Selvaraj, S.P.,Li, C.C.,Lin, P.Y.,Huang, Y.P.,Chang, C.F.,You, M.F.,Chen, J.Y.
Antimicrobial peptide-induced inner membrane hyperpolarization is associated with antibiotic sensitization and attenuated MIC escalation in multidrug-resistant Gram-negative pathogens.
NPJ Antimicrob Resist, 4:-, 2026

PubMed Abstract: Antimicrobial resistance and dysregulated inflammation drive mortality in multidrug-resistant (MDR) sepsis. We evaluated the cationic peptide TP2-5 as a low-dose antibiotic adjuvant. At sub-MIC concentrations, TP2-5 enhanced antibiotic susceptibility of MDR E. coli in broth and 50% human serum, and in combination with antibiotics was associated with attenuated MIC escalation during 21-day serial passage. Membrane potential assays and cryo-electron tomography showed envelope perturbation characterized by inner-membrane hyperpolarization. This biophysical state was temporally associated with preferential interactions with lipopolysaccharide (LPS) and anionic phospholipids rather than nonspecific permeabilization. TP2-5 neutralized LPS and reduced TLR4-dependent cytokine production. In our murine polymicrobial CLP sepsis model, TP2-5 alone or with meropenem achieved 100% survival, accompanied by reduced bacterial burden and systemic inflammatory cytokines, consistent with combined antibacterial and host-directed effects, supporting a multifunctional adjuvant profile. This study did not measure bacterial membrane potential in vivo, and the causal role of hyperpolarization in protection or attenuated MIC escalation remains to be determined.

PubMed: 42062577
DOI: 10.1038/s44259-026-00210-x

Experimental method

SOLUTION NMR