Abstract

Pneumonia remains a leading global cause of mortality across all age groups, with multidrug-resistant (MDR) pathogens presenting a major treatment challenge (WHO, 2021). Beyond their roles in immune regulation, certain chemokines exhibit intrinsic antimicrobial properties. We recently developed an 8-mer antimicrobial peptide (AMP), named peptide D8, which is derived from the N-terminal region of the human chemokine CXCL10. Peptide D8 demonstrates broad-spectrum bactericidal activity, including efficacy against diverse MDR pathogens. It is proteolytically stable, non-hemolytic, and non-toxic toward human cells in vitro. To evaluate its therapeutic potential in vivo, the efficacy of peptide D8 was tested via different routes of administration in two separate murine models of Klebsiella pneumoniae infection: topical D8 administration in a wound infection model and systemic administration via intraperitoneal D8 injection in a pneumonia model. In each case, peptide D8 administration significantly reduced host mortality. These findings highlight chemokine-derived AMPs as a promising new class of anti-infective agents. By combining host-derived origin, stability, and broad efficacy, peptide D8 represents a potential innovative therapy for drug-resistant bacterial wound and lung infections.

Keywords: chemokine, CXCL10, antimicrobial peptides, multidrug resistance