Tryptophan end-tagging of antimicrobial peptides for increased potency against Pseudomonas aeruginosa.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1392457
- author
- Pasupuleti, Mukesh LU ; Chalupka, Anna LU ; Mörgelin, Matthias LU ; Schmidtchen, Artur LU and Malmsten, Martin LU
- organization
- publishing date
- 2009
- 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
- pmid:19345721
- 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
- 2016-04-04 09:10:44
- date last changed
- 2022-01-29 08:39:10
@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}},
doi = {{10.1016/j.bbagen.2009.03.029}},
volume = {{1790}},
year = {{2009}},
}