Structure and mode of action of cyclic lipopeptide pseudofactin II with divalent metal ions

Abstract

The interaction of natural lipopeptide pseudofactin II with a series of doubly charged metal cations was examined by matrix-assisted laser-desorption ionization-time of flight (MALDI-TOF) mass spectrometry and molecular modelling. The molecular modelling for metal-pseudofactin II provides information on the metal-peptide binding sites. Overall, Mg(2+), Ca(2+) and Zn(2+) favor the association with oxygen atoms spanning the peptide backbone, whereas Cu(2+) is coordinated by three nitrogens. Circular dichroism (CD) results confirmed that Zn(2+) and Cu(2+) can disrupt the secondary structure of pseudofactin II at high concentrations, while Ca(2+) and Mg(2+) did not essentially affect the structure of the lipopeptide. Interestingly, our results showed that the addition of Zn(2+) and Cu(2+) helped smaller micelles to form larger micellar aggregates. Since pseudofactin II binds metals, we tested whether this phenomena was somehow related to its antimicrobial activity against Staphylococcus epidermidis and Proteus mirabilis. We found that the antimicrobial effect of pseudofactin II was increased by supplementation of culture media with all tested divalent metal ions. Finally, by using Gram-positive and Gram-negative bacteria we showed that the higher antimicrobial activity of metal complexes of pseudofactin II is attributed to the disruption of the cytoplasmic membrane.

Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A

“…This cyclic peptide does not possess the peculiarity of some Zn 2+ chelating peptides as Cys residues [37], or thiazole and oxazoline rings [38]. However the pseudofactin II, a cyclic lipo-octapeptide, has recently been shown to chelate Zn 2+ via carbonyl oxygens from the main backbone in a 1:1 stoichiometry [39]. It might also be the case for Laxaphycin B.…”

Lipopeptide-Induced Suicidal Erythrocyte Death Correlates with the Degree of Acylation

“…One of the most aggressive cyclic lipopeptides is surfactin. It has a high detergent effect by inserting its fatty acid chain into the lipid bilayer [89, 90]. Its cell destruction is indiscriminate, and it attacks also erythrocytes with deadly efficiency.…”

“…Cyclic lipopeptides constitute a structurally diverse group of metabolites produced by various bacterial and fungal genera via non-ribosomal pathways [88]. Structurally they are amphiphilic molecules that comprise both hydrophobic and hydrophilic moieties; in this respect they resemble our Lpp.…”

“…Its cell destruction is indiscriminate, and it attacks also erythrocytes with deadly efficiency. Pseudofactins inhibit bacterial adhesion (the first stage of biofilm formation) but have also antiproliferative effects on mammalian cells [88]. Polymyxin B has antibacterial activity against Gram-negative bacteria by binding selectively to lipopolysaccharide (LPS) [91].…”

Direct quantification of lipopeptide biosurfactants in biological samples via HPLC and UPLC-MS requires sample modification with an organic solvent

“…The physiochemical and biological properties of PF2 were investigated. PF2 exhibits good emulsification activity in comparison to synthetic detergents (Janek et al 2010), as well as antimicrobial, antiadhesive, and antibiofilm activity against several uropathogenic bacterial strains and Candida albicans (Janek et al 2012; Biniarz et al 2015a; Janek et al 2016). Moreover, PF2 exhibits strong antitumor activity (Janek et al 2013).…”