Killer Peptide: An antibody-derived self-assembling peptide bridging antimicrobial and host-defense mechanisms

Abstract Antimicrobial resistance and persistent biofilm-associated infections continue to drive the search for peptide-based anti-infective agents with mechanisms distinct from conventional antibiotics. Killer Peptide (KP) is an antibody-derived decapeptide originally identified through yeast killer toxin mimicry studies and has emerged as a distinctive example of a multifunctional bioactive peptide. Experimental studies have reported particularly strong antifungal activity, together with activity against selected bacteria, biofilms, viruses, and protozoa, as well as immunomodulatory effects in preclinical models. Mechanistically, KP appears to act through a multistep process involving target-surface recognition, cellular internalization, induction of intracellular stress pathways, and reversible self-assembly into fibrillar structures that may support localized peptide retention. In parallel, KP has been reported to influence innate and adaptive immune responses, suggesting potential host-defense-enhancing properties. In this review, we critically reassess two decades of KP research, covering its molecular origin, structural features, antimicrobial spectrum, mechanisms of action, engineered derivatives, and translational prospects. We also examine current limitations, including the relatively narrow evidence base, incomplete pharmacological characterization, and the need for independent validation across disease models. KP represents a useful conceptual framework for the development of next-generation multifunctional peptides integrating antimicrobial, pathogen-triggered assembly, and immunomodulatory properties.