Modulating reconstituted high density lipoprotein functionality to target the Pseudomonas aeruginosa quorum sensing system
| Autor: | Silvana Bioletto, Karl Perron, Sara Deakin, Richard W. James, Verena Ducret |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Gene Expression
Peptide 030204 cardiovascular system & hematology Protein Engineering chemistry.chemical_compound 0302 clinical medicine Pseudomonas aeruginosa/drug effects/growth & development/metabolism 4-Butyrolactone Lactonase General Pharmacology Toxicology and Pharmaceutics Aryldialkylphosphatase/genetics/metabolism chemistry.chemical_classification ddc:616 0303 health sciences ddc:615 biology Hydrolysis Quorum Sensing Liver/chemistry/enzymology Quorum Sensing/drug effects General Medicine ddc:580 Liver Biochemistry Pseudomonas aeruginosa lipids (amino acids peptides and proteins) Lipoproteins HDL/genetics/metabolism/pharmacology Lipoproteins HDL Signal peptide Recombinant Fusion Proteins Homoserine Recombinant Fusion Proteins/genetics/metabolism/pharmacology Virulence 4-Butyrolactone/analogs & derivatives/chemistry Protein Sorting Signals General Biochemistry Genetics and Molecular Biology Culture Media Conditioned/pharmacology 03 medical and health sciences Humans Secretion 030304 developmental biology Aryldialkylphosphatase Protein Sorting Signals/genetics Biofilm nutritional and metabolic diseases Quorum sensing HEK293 Cells chemistry Culture Media Conditioned biology.protein |
| Zdroj: | Life Sciences, Vol. 112, No 1-2 (2014) pp. 68-73 LIFE SCIENCES |
| ISSN: | 0024-3205 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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