Journal article
Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1
The Journal of clinical investigation, Vol.118(9), pp.3123-3131
09/02/2008
DOI: 10.1172/JCI35147
PMCID: PMC2515384
PMID: 18704198
Abstract
Pseudomonas aeruginosa
uses quorum sensing, an interbacterial communication system, to regulate gene expression. The signaling molecule
N
-3-oxododecanoyl homoserine lactone (3OC12-HSL) is thought to play a central role in quorum sensing. Since 3OC12-HSL can be degraded by paraoxonase (PON) family members, we hypothesized that PONs regulate
P. aeruginosa
virulence in vivo. We chose
Drosophila melanogaster
as our model organism because it has been shown to be a tractable model for investigating host-pathogen interactions and lacks PONs. By using quorum-sensing–deficient
P. aeruginosa
, synthetic acyl-HSLs, and transgenic expression of human PON1, we investigated the role of 3OC12-HSL and PON1 on
P. aeruginosa
virulence. We found that
P. aeruginosa
virulence in flies was dependent upon 3OC12-HSL. PON1 transgenic flies expressed enzymatically active PON1 and thereby exhibited arylesterase activity and resistance to organophosphate toxicity. Moreover, PON1 flies were protected from
P. aeruginosa
lethality, and protection was dependent on the lactonase activity of PON1. Our findings show that PON1 can interfere with quorum sensing in vivo and provide insight into what we believe is a novel role for PON1 in the innate immune response to quorum-sensing–dependent pathogens. These results raise intriguing possibilities about human-pathogen interactions, including potential roles for PON1 as a modifier gene and for PON1 protein as a regulator of normal bacterial florae, a link between infection/inflammation and cardiovascular disease, and a potential therapeutic modality.
Details
- Title: Subtitle
- Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1
- Creators
- David A Stoltz - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAEgon A Ozer - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAPeter J Taft - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAMarilyn Barry - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USALei Liu - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAPeter J Kiss - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAThomas O Moninger - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAMatthew R Parsek - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAJoseph Zabner - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.118(9), pp.3123-3131
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI35147
- PMID
- 18704198
- PMCID
- PMC2515384
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 09/02/2008
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984025302602771
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