Design of a multimodal synthetic peptide antibiotic derived from human cathelicidin.

Comprehensive preclinical evaluation of an inverso peptide derivative

“This study provides the first comprehensive preclinical validation of an inverso LL-37-derived peptide, demonstrating that d-GK17 displays potent broad-spectrum antimicrobial, antibiofilm, and immunomodulatory effects while maintaining stability in serum and wound environments with a low propensity for resistance development.”

Multidrug-resistant Acinetobacter baumannii, other bacterial strains, human cell lines, and murine infection models

“We present the first comprehensive preclinical evaluation of d-GK17, detailing its antibacterial, antibiofilm, and immunomodulatory properties, as well as its mechanism of action, stability in complex biological environments, and therapeutic efficacy in a mouse model of A. baumannii infection.”

Five mice per group in animal models; three independent biological replicates for in vitro assays

“The experiments were performed using five mice per group.”

In vitro assays up to 40 days for resistance studies; in vivo models assessed at 2 and 4 days post-infection

“Serial passaging of A. baumannii ATCC 19606 over 40 days revealed no significant development of antimicrobial resistance to d-GK17, GK-17, or polymyxin B.”

d-GK17 exhibits potent broad-spectrum antimicrobial activity and stability in serum

“d-GK17 displays potent broad-spectrum antimicrobial, antibiofilm, and immunomodulatory effects while maintaining stability in serum and wound environments with a low propensity for resistance development.”

d-GK17 effectively disrupts biofilm architecture and kills biofilm-encased cells

“It also surpasses conventional antibiotics and its L-amino acid counterpart in disrupting established biofilms, collapsing biofilm architecture, and killing biofilm-encased cells.”

d-GK17 reduces bacterial load in murine infection models without observed toxicity

“In murine infection models, d-GK17 significantly reduces bacterial load over extended periods without toxicity.”

Lack of histological and inflammatory assessments in vivo; need for further evaluation of long-term safety and immunogenicity

“We acknowledge that additional histological and inflammatory assessments would further strengthen the translational interpretation of these in vivo findings, and we explicitly recognize this as a limitation of the present study.”