Ultrashort antibacterial and antifungal lipopeptides

TLDR

Host‑defense cationic antimicrobial peptides (~12–50 aa) protect all organisms, whereas bacterial and fungal lipopeptides—short anionic peptides bearing lipophilic chains—are produced only during cultivation. The study reports on the design and potent activity of ultrashort antibacterial and antifungal lipopeptides. Attaching an aliphatic chain to inert cationic D,L tetrapeptides endows them with potent activity against diverse, including resistant, microorganisms, with specificity governed by peptide sequence and chain length, and despite their short length they permeate and disrupt membranes, making these simple, cost‑effective lipopeptides promising innate‑immunity‑mimicking antimicrobials.

Abstract

Host-defense cationic antimicrobial peptides ( approximately 12-50 aa long) play an essential protective role in the innate immune system of all organisms. Lipopeptides, however, are produced only in bacteria and fungi during cultivation, and they are composed of specific lipophilic moieties attached to anionic peptides (six to seven amino acids). Here we report the following. (i) The attachment of an aliphatic chain to otherwise inert, cationic D,L tetrapeptides endows them with potent activity against various microorganisms including antibiotic resistance strains. (ii) Cell specificity is determined by the sequence of the short peptidic chain and the length of the aliphatic moiety. (iii) Despite the fact that the peptidic chains are very short, their mode of action involves permeation and disintegration of membranes, similar to that of many long antimicrobial peptides. Besides adding important information on the parameters necessary for host-defense lipopeptides to kill microorganisms, the simple composition of these lipopeptides and their diverse specificities should make them economically available, innate immunity-mimicking antimicrobial and antifungal compounds for various applications.