New strategies for novel antibiotics: peptides targeting bacterial cell membranes

Abstract

Abstract. Membranes are targets of host defence or antimicrobial peptides, effector molecules of innate immunity that evolved in nature to contend with invaders as an active system of defence. The different physicochemical properties of the lipids found in biological membranes allow antimicrobial peptides to discriminate between bacterial and mammalian cell membranes. Such cationic amphipathic peptides will interact predominantly with negatively charged lipids exposed on the outer leaflet of bacterial cell membranes. The molecular mechanism(s) of membrane rupture mutually depends on the nature of the peptide and membrane lipid composition. Biophysical studies demonstrated a complex behavior in terms of membrane perturbation, which can range from pore formation to micellization (carpet model). Peptides aligned parallel to the membrane surface can induce a quasiinterdigitated structure in the gel phase, while depending on the hydrophobic matching of the lipid bilayer core and the peptide membrane thinning or thickening can be observed in the fluid phase. As a consequence, besides of peptide-lipid pores, formation of peptide-enriched membrane domains and promotion of cubic structures can be observed, which adversely affect membrane integrity and function. A strategy using the membrane damaging properties of these peptides will form the basis for the development of such peptides as potential novel antibiotic drugs.

Membrane potential is important for bacterial cell division

“…Many of these antibiotics are targeting the cell membrane and dissipate the membrane potential (33). Incubation of B. subtilis with the natural antibiotic nisin results in elongated cells and minicells, indicative of a malfunctioning Min system (34).…”

The black soldier fly, Hermetia illucens – a promising source for sustainable production of proteins, lipids and bioactive substances

“…The latter involve the production of AMPs that are synthesized in the fat body and subsequently secreted into the hemolymph [39,40]. In general, AMPs can serve as effective antibiotics or fungicides that mainly attack the cell envelope, especially the cell membrane and also affect intracellular targets of microorganisms which subsequently lead to cell death [41][42][43]. Several recent studies that reported the antimicrobial activity of the larvae hemolymph and maggot extract as well as of secretions, are promising for the development of new therapeutically valuable antibiotics, particularly in the defense of multi-resistant "super bugs" (e.g.…”

Antimicrobial lipids: Emerging effector molecules of innate host defense

“…These specialized regions are referred to as lipid rafts and caveolae [10][11][12] . There are substantial differences in the phospholipid composition of bacterial and mammalian cell membranes, likely contributing to the preferential action of host defense molecules against bacterial targets [13][14][15] . Furthermore, lipids liberated from cellular membranes have been found to be strong modulators of inflammation.…”