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Tryptophan end-tagging of antimicrobial peptides for increased potency against Pseudomonas aeruginosa.

Pasupuleti, Mukesh LU ; Chalupka, Anna LU ; Mörgelin, Matthias LU ; Schmidtchen, Artur LU and Malmsten, Martin (2009) In Biochimica et Biophysica Acta. General Subjects 1790(8). p.800-808
Abstract
BACKGROUND: Due to increasing antibiotics resistance, antimicrobial peptides (AMPs) are receiving increased attention. Pseudomonas aeruginosa is a major pathogen in this context, involved, e.g., in keratitis and wound infections. Novel bactericidal agents against this pathogen are therefore needed. METHODS: Bactericidal potency was monitored by radial diffusion, viable count, and minimal inhibitory concentration assays, while toxicity was probed by hemolysis. Mechanistic information was obtained from assays on peptide-induced vesicle disruption and lipopolysaccharide binding. RESULTS: End-tagging by hydrophobic amino acids yields increased potency of AMPs against P. aeruginosa, irrespective of bacterial proteinase production. Exemplifying... (More)
BACKGROUND: Due to increasing antibiotics resistance, antimicrobial peptides (AMPs) are receiving increased attention. Pseudomonas aeruginosa is a major pathogen in this context, involved, e.g., in keratitis and wound infections. Novel bactericidal agents against this pathogen are therefore needed. METHODS: Bactericidal potency was monitored by radial diffusion, viable count, and minimal inhibitory concentration assays, while toxicity was probed by hemolysis. Mechanistic information was obtained from assays on peptide-induced vesicle disruption and lipopolysaccharide binding. RESULTS: End-tagging by hydrophobic amino acids yields increased potency of AMPs against P. aeruginosa, irrespective of bacterial proteinase production. Exemplifying this by two peptides from kininogen, GKHKNKGKKNGKHNGWK and KNKGKKNGKH, potency increased with tag length, correlating to more efficient bacterial wall and vesicle rupture, and to more pronounced P. aeruginosa lipopolysaccharide binding. End-tag effects remained at high electrolyte concentration and in the presence of plasma or anionic macromolecular scavengers. The tagged peptides displayed stability against P. aeruginosa elastase, and were potent ex vivo, both in a contact lens model and in a skin wound model. GENERAL SIGNIFICANCE: End-tagging, without need for post-peptide synthesis modification, may be employed to enhance AMP potency against P. aeruginosa at maintained limited toxicity. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Biochimica et Biophysica Acta. General Subjects
volume
1790
issue
8
pages
800 - 808
publisher
Elsevier
external identifiers
  • WOS:000268264200008
  • PMID:19345721
  • Scopus:67649361736
ISSN
0304-4165
DOI
10.1016/j.bbagen.2009.03.029
language
English
LU publication?
yes
id
93c1c700-bdf6-41b0-acbf-e649992c03c1 (old id 1392457)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19345721?dopt=Abstract
date added to LUP
2009-05-04 14:36:14
date last changed
2017-01-01 07:44:02
@article{93c1c700-bdf6-41b0-acbf-e649992c03c1,
  abstract     = {BACKGROUND: Due to increasing antibiotics resistance, antimicrobial peptides (AMPs) are receiving increased attention. Pseudomonas aeruginosa is a major pathogen in this context, involved, e.g., in keratitis and wound infections. Novel bactericidal agents against this pathogen are therefore needed. METHODS: Bactericidal potency was monitored by radial diffusion, viable count, and minimal inhibitory concentration assays, while toxicity was probed by hemolysis. Mechanistic information was obtained from assays on peptide-induced vesicle disruption and lipopolysaccharide binding. RESULTS: End-tagging by hydrophobic amino acids yields increased potency of AMPs against P. aeruginosa, irrespective of bacterial proteinase production. Exemplifying this by two peptides from kininogen, GKHKNKGKKNGKHNGWK and KNKGKKNGKH, potency increased with tag length, correlating to more efficient bacterial wall and vesicle rupture, and to more pronounced P. aeruginosa lipopolysaccharide binding. End-tag effects remained at high electrolyte concentration and in the presence of plasma or anionic macromolecular scavengers. The tagged peptides displayed stability against P. aeruginosa elastase, and were potent ex vivo, both in a contact lens model and in a skin wound model. GENERAL SIGNIFICANCE: End-tagging, without need for post-peptide synthesis modification, may be employed to enhance AMP potency against P. aeruginosa at maintained limited toxicity.},
  author       = {Pasupuleti, Mukesh and Chalupka, Anna and Mörgelin, Matthias and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {0304-4165},
  language     = {eng},
  number       = {8},
  pages        = {800--808},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta. General Subjects},
  title        = {Tryptophan end-tagging of antimicrobial peptides for increased potency against Pseudomonas aeruginosa.},
  url          = {http://dx.doi.org/10.1016/j.bbagen.2009.03.029},
  volume       = {1790},
  year         = {2009},
}