Joseph Zabner and colleagues, at the University of Iowa Carver College of Medicine, Iowa City, have used a fruit fly (Drosophila) model of infection to provide new insight into the molecular mechanisms underlying the virulence of the bacterium Pseudomonas aeruginosa, which is a major cause of infections in individuals who are hospitalized, have burn wounds, or have cystic fibrosis.
P. aeruginosa communicate with each other via a process known as quorum sensing. Previous studies have suggested that P. aeruginosa quorum-sensing molecules (such as 3OC12-HSL) are important for virulence and that human proteins known as PONs, which are able to destroy quorum-sensing molecules, contribute to protection from lethal P. aeruginosa infection.
For various reasons it has been hard to develop a model system in which to test this hypothesis. So, the authors turned to a Drosophila model of infection, as these flies have no PONs proteins of their own. Initial studies established that P. aeruginosa infection kills Drosophila and that this depends on the ability of the P. aeruginosa to produce 3OC12-HSL.
However, if the Drosophila were engineered to express human PON1 they were protected from killing following P. aeruginosa infection.
These data indicate that PON1 is important for protection against lethal P. aeruginosa infection via its ability to interfere with quorum sensing, and further suggest that targeting quorum-sensing molecules or modulating PON function might provide new approaches to therapy.
- Stoltz et al. Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1
. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI35147
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