Lipid segregation explains selective toxicity of a series of fragments derived from the human cathelicidin LL-37

Raquel F. Epand, Guangshun Wang, Bob Berno, Richard M. Epand

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The only human cathelicidin, the 37-residue peptide LL-37, exhibits antimicrobial activity against both gram-positive and gram-negative bacteria. We studied the ability of several fragments of LL-37, exhibiting different antimicrobial activities, to interact with membranes whose compositions mimic the cytoplasmic membranes of gram-positive or of gram-negative bacteria. These fragments are as follows: KR-12, the smallest active segment of LL-37, with the sequence KRIVQRIKDFLR, which exhibits antimicrobial activity only against gram-negative bacteria; a slightly smaller peptide, RI-10, missing the two cationic residues at the N and C termini of KR-12, which has been shown not to have any antimicrobial activity; a longer peptide, GF-17, which shows antimicrobial activity against gram-positive as well as gram-negative bacteria; and GF-17D3, with 3 D-amino-acid residues, which is also selective only for gram-negative bacteria. Those fragments with the capacity to cluster anionic lipids away from zwitterionic lipids in a membrane exhibit selective toxicity toward bacteria containing zwitterionic as well as anionic lipids in their cytoplasmic membranes but not toward bacteria with only anionic lipids. This finding allows for the prediction of the bacterial-species selectivity of certain agents and paves the way for designing new antimicrobials targeted specifically toward gram-negative bacteria.

Original languageEnglish (US)
Pages (from-to)3705-3714
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number9
DOIs
StatePublished - Sep 21 2009

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Gram-Negative Bacteria
Lipids
Cell Membrane
Bacteria
Peptides
Membranes
CAP18 lipopolysaccharide-binding protein
Amino Acids

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Lipid segregation explains selective toxicity of a series of fragments derived from the human cathelicidin LL-37. / Epand, Raquel F.; Wang, Guangshun; Berno, Bob; Epand, Richard M.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 9, 21.09.2009, p. 3705-3714.

Research output: Contribution to journalArticle

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