In-Membrane Nanostructuring of Cationic Amphiphiles
Affects Their Antimicrobial Efficacy and Cytotoxicity: A Comparison
Study between a De Novo Antimicrobial Lipopeptide and Traditional
Biocides
posted on 2022-05-19, 16:13authored byKe Fa, Huayang Liu, Haoning Gong, Lin Zhang, Mingrui Liao, Xuzhi Hu, Daniela Ciumac, Peixun Li, John Webster, Jordan Petkov, Robert K. Thomas, Jian Ren Lu
Cationic biocides
have been widely used as active ingredients in
personal care and healthcare products for infection control and wound
treatment for a long time, but there are concerns over their cytotoxicity
and antimicrobial resistance. Designed lipopeptides are potential
candidates for alleviating these issues because of their mildness
to mammalian host cells and their high efficacy against pathogenic
microbial membranes. In this study, antimicrobial and cytotoxic properties
of a de novo designed lipopeptide, CH3(CH2)12CO-Lys-Lys-Gly-Gly-Ile-Ile-NH2 (C14KKGGII), were assessed against that of two traditional cationic biocides
CnTAB (n = 12 and 14),
with different critical aggregation concentrations (CACs). C14KKGGII was shown to be more potent against both bacteria and fungi
but milder to fibroblast host cells than the two biocides. Biophysical
measurements mimicking the main features of microbial and host cell
membranes were obtained for both lipid monolayer models using neutron
reflection and small unilamellar vesicles (SUVs) using fluorescein
leakage and zeta potential changes. The results revealed selective
binding to anionic lipid membranes from the lipopeptide and in-membrane
nanostructuring that is distinctly different from the co-assembly
of the conventional CnTAB. Furthermore,
CnTAB binding to the model membranes showed
low selectivity, and its high cytotoxicity could be attributed to
both membrane lysis and chemical toxicity. This work demonstrates
the advantages of the lipopeptides and their potential for further
development toward clinical application.