Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity

Sebastien Farnaud; Claire Spiller; Laura C. Moriarty; Alpesh Patel; Vanya Gant; Edward W. Odell; Robert W. Evans

doi:10.1016/j.femsle.2004.01.039

Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity

Sebastien Farnaud
, Claire Spiller
, Laura C. Moriarty
, Alpesh Patel
, Vanya Gant
, Edward W. Odell
, Robert W. Evans

King's College London
Royal Free London NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

87 Citations (Scopus)

Abstract

Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence and peptides corresponding to chimeras of human and bovine sequences. None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity. Results obtained for the same assays performed with LPS mutants suggest that lipid A is not the main binding site for lactoferricin which interacts first with the negative charges present in the inner core. Computer modelling of the most active peptides led to a model in which positively charged residues of the cationic peptide interact with negative charges carried by the LPS to disorganise the structure of the outer membrane and facilitate the approach of tryptophan residues to the lipid A in order to promote hydrophobic interactions.

Original language	English
Pages (from-to)	193-199
Number of pages	7
Journal	FEMS Microbiology Letters
Volume	233
Issue number	2
DOIs	https://doi.org/10.1016/j.femsle.2004.01.039
Publication status	Published - 1 Apr 2004
Externally published	Yes

Funding

We are grateful to Professor C.R. Raetz from Duke University Medical Center, Durham, for providing the lipid A mutants strains. Sebastien Farnaud was funded by a Wellcome Trust Project Grant (Ref. 059414); Claire Spiller was funded by a grant from King's College London School of Biomedical Sciences Summer Studentship Scheme; Laura Moriarty was funded by a grant from the Nutricia Research Foundation; Alpesh Patel was funded by a studentship from the BBSRC.

Keywords

Cationic antimicrobial peptides
Lactoferricin
Lactoferrin
LPS
MBC

ASJC Scopus subject areas

Microbiology
Molecular Biology
Genetics

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10.1016/j.femsle.2004.01.039

Cite this

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title = "Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity",

abstract = "Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence and peptides corresponding to chimeras of human and bovine sequences. None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity. Results obtained for the same assays performed with LPS mutants suggest that lipid A is not the main binding site for lactoferricin which interacts first with the negative charges present in the inner core. Computer modelling of the most active peptides led to a model in which positively charged residues of the cationic peptide interact with negative charges carried by the LPS to disorganise the structure of the outer membrane and facilitate the approach of tryptophan residues to the lipid A in order to promote hydrophobic interactions.",

keywords = "Cationic antimicrobial peptides, Lactoferricin, Lactoferrin, LPS, MBC",

author = "Sebastien Farnaud and Claire Spiller and Moriarty, \{Laura C.\} and Alpesh Patel and Vanya Gant and Odell, \{Edward W.\} and Evans, \{Robert W.\}",

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AU - Farnaud, Sebastien

AU - Spiller, Claire

AU - Moriarty, Laura C.

AU - Patel, Alpesh

AU - Gant, Vanya

AU - Odell, Edward W.

AU - Evans, Robert W.

PY - 2004/4/1

Y1 - 2004/4/1

N2 - Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence and peptides corresponding to chimeras of human and bovine sequences. None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity. Results obtained for the same assays performed with LPS mutants suggest that lipid A is not the main binding site for lactoferricin which interacts first with the negative charges present in the inner core. Computer modelling of the most active peptides led to a model in which positively charged residues of the cationic peptide interact with negative charges carried by the LPS to disorganise the structure of the outer membrane and facilitate the approach of tryptophan residues to the lipid A in order to promote hydrophobic interactions.

AB - Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence and peptides corresponding to chimeras of human and bovine sequences. None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity. Results obtained for the same assays performed with LPS mutants suggest that lipid A is not the main binding site for lactoferricin which interacts first with the negative charges present in the inner core. Computer modelling of the most active peptides led to a model in which positively charged residues of the cationic peptide interact with negative charges carried by the LPS to disorganise the structure of the outer membrane and facilitate the approach of tryptophan residues to the lipid A in order to promote hydrophobic interactions.

KW - Cationic antimicrobial peptides

KW - Lactoferricin

KW - Lactoferrin

KW - LPS

KW - MBC

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Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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