Antimicrobial peptides (AMPs) have great potential in treating multi-drug resistant bacterial infections. The antimicrobial activity of d-enantiomers is significantly higher than l-enantiomers and sometimes selectively enhanced against Gram-positive bacteria. Unlike phospholipids in the bacterial plasma membrane, the role of other bacterial cell envelop components is often overlooked in the mode of action of AMPs. In this work, we explored the structural interactions between the main different structural components in Gram-negative/Gram-positive bacteria and the two enantiomers of a designer AMP, GL13K. We observed that both l-GL13K and d-GL13K formed self-assembled amyloid-like nanofibrils when the peptides interacted with lipopolysaccharide and lipoteichoic acid, components of the outer membrane of Gram-negative bacteria and cell wall of Gram-positive bacteria, respectively. Another cell wall component, peptidoglycan, showed strong interactions exclusively with d-GL13K and formed distinct laminar structures. This specific interaction between peptidoglycans and d-GL13K might contribute to the enhanced activity of d-GL13K against Gram-positive bacteria as they have a much thicker peptidoglycan layer than Gram-negative bacteria. A better understanding of the specific role of bacterial cell envelop components in the AMPs mechanism of action can guide the design of more effective Gram-selective AMPs.
|Original language||English (US)|
|Journal||Journal of Peptide Science|
|Early online date||Jan 25 2021|
|State||Published - Jan 25 2021|
Bibliographical noteFunding Information:
This research was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health (grant R01DE026117 to C. A.) and the National Institutes of Health's National Center for Advancing Translational Sciences (Translational Research Development Program [TRDP] award to Z. Y. from grant UL1TR002494). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program.
© 2021 European Peptide Society and John Wiley & Sons, Ltd.
- Gram-selective killing
- antimicrobial peptides
- lipoteichoic acid
- peptide chirality
PubMed: MeSH publication types
- Journal Article