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Life Sci. 2014 Sep 1;112(1-2):68-73. doi: 10.1016/j.lfs.2014.07.028. Epub 2014 Jul 30.

Modulating reconstituted high density lipoprotein functionality to target the Pseudomonas aeruginosa quorum sensing system.

Author information

1
Clinical Diabetes Unit, Department of Internal Medicine, Medical Faculty, University of Geneva, Geneva, Switzerland.
2
Microbiology Unit, Department of Botany and Plant Biology, Sciences III, University of Geneva, Geneva, Switzerland.
3
Clinical Diabetes Unit, Department of Internal Medicine, Medical Faculty, University of Geneva, Geneva, Switzerland. Electronic address: Richard.James@hcuge.ch.

Abstract

AIMS:

The synthetic counterparts of serum high density lipoproteins (HDL; reconstituted HDL, reHDL) are assuming increasing importance as a therapeutic vector. They circulate not only in blood, but also outside the vascular compartment giving access to all body tissues. Presently, the therapeutic use of reHDL exploits inherent HDL functions. Our aim was to determine if HDL functionality could be modulated by attaching peptides not normally associated with the complex.

MAIN METHODS:

A peptide chimera was designed by linking the signal peptide of the HDL-associated enzyme paraoxonase-1 (PON1) to the coding region for the intracellular enzyme paraoxonase-2 (PON2).

KEY FINDINGS:

The signal peptide modified the properties of PON2, promoting its secretion from cells and binding to HDL. Enzyme activity of the chimera protein was highly stable. Conditioned HDL showed the functions of PON2 in its ability to hydrolyse typical PON2 substrates, namely homoserine lactones. Further in vitro studies showed that conditioned HDL was able to reduce the virulence of Pseudomonas aeruginosa. Both biofilm formation and the activation of the quorum sensing systems las and rhl, responsible for bacterial virulence, were significantly reduced.

SIGNIFICANCE:

The study provides proof of principal that the signal peptide of PON1 can be used to attach peptides to HDL and thus modulate HDL function. They may provide a vector that is ubiquitously distributed in extracellular body fluids for designing therapeutic strategies to address different pathophysiological states.

KEYWORDS:

HDL; Lactonase; Paraoxonase; Reconstituted

PMID:
25086378
DOI:
10.1016/j.lfs.2014.07.028
[Indexed for MEDLINE]

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