Investigation of the role of tryptophan residues in cationic antimicrobial peptides to determine the mechanism of antimicrobial action
Article first published online: 19 JUN 2013
© 2013 The Society for Applied Microbiology
Journal of Applied Microbiology
Volume 115, Issue 3, pages 663–672, September 2013
How to Cite
Bi, X., Wang, C., Ma, L., Sun, Y. and Shang, D. (2013), Investigation of the role of tryptophan residues in cationic antimicrobial peptides to determine the mechanism of antimicrobial action. Journal of Applied Microbiology, 115: 663–672. doi: 10.1111/jam.12262
- Issue published online: 14 AUG 2013
- Article first published online: 19 JUN 2013
- Accepted manuscript online: 27 MAY 2013 08:31AM EST
- Manuscript Accepted: 18 MAY 2013
- Manuscript Revised: 4 MAY 2013
- Manuscript Received: 18 FEB 2013
- National Natural Science Foundation of China. Grant Numbers: 31272314, 81202448
- Natural Science Foundation of Liaoning. Grant Number: 201202121
- Program for Liaoning Innovative Research Team in University. Grant Number: LT2012019
- antimicrobial activities;
- calcein-loaded liposomes;
To understand the effects of Trp residues in linear antimicrobial peptides with α-helical conformations on cell permeation ability and membrane transduction efficacy.
Methods and Results
A series of L-K6 analogues were designed and synthesized by replacing Ile or Leu with Trp at different positions on the hydrophobic face of L-K6. The antimicrobial and haemolytic activity and secondary structure of the designed Trp-containing peptides were assessed. In addition, the role of Trp in membrane disruption for these designed peptides was investigated. I1W, I4W and L5W demonstrated stronger activity than the other peptides against both Gram-positive and Gram-negative bacteria. All of the tested peptides preferentially interacted with negatively charged vesicles composed of phosphatidylglycerol (PG)/cardiolipin (CL) or PG/CL/phosphatidylethanolamine, and, to a lesser extent, with zwitterionic vesicles. I1W, I4W and L5W caused calcein release at 2·5 μmol l−1.
The position of Trp, rather than the number of Trp residues, in these peptides was an important factor in the antimicrobial activity. Trp residues were deeply inserted into negatively charged membranes but were largely exposed in aqueous buffer solution.
Significance and Impact of the Study
These Trp-containing peptides may represent good candidates for new antibiotic agents and for use in new therapeutic approaches.