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Expression of human paraoxonase 1 decreases superoxide levels and alters bacterial colonization in the gut of Drosophila melanogaster
Journal article   Open access   Peer reviewed

Expression of human paraoxonase 1 decreases superoxide levels and alters bacterial colonization in the gut of Drosophila melanogaster

Alejandro A Pezzulo, Emma E Hornick, Michael V Rector, Miriam Estin, Anna C Reisetter, Peter J Taft, Stephen C Butcher, A Brent Carter, J Robert Manak, David A Stoltz, …
PloS one, Vol.7(8), pp.e43777-e43777
2012
DOI: 10.1371/journal.pone.0043777
PMCID: PMC3431398
PMID: 22952763
url
https://doi.org/10.1371/journal.pone.0043777View
Published (Version of record) Open Access

Abstract

Paraoxonases (PON) are a family of proteins (PON1, 2 and 3) with multiple enzymatic activities. PON1 interferes with homoserine lactone-mediated quorum sensing in bacteria and with reactive oxygen species (ROS) in humans and mice. PON1 gene mutations have been linked to multiple traits, including aging, and diseases of the cardiovascular, nervous and gastrointestinal system. The overlapping enzymatic activities in the PON family members and high linkage disequilibrium rates within their polymorphisms confound animal and human studies of PON1 function. In contrast, arthropods such as Drosophila melanogaster have no PON homologs, resulting in an ideal model to study interactions between PON genotype and host phenotypes. We hypothesized that expression of PON1 in D. melanogaster would alter ROS. We found that PON1 alters expression of multiple oxidative stress genes and decreases superoxide anion levels in normal and germ-free D. melanogaster. We also found differences in the composition of the gut microbiota, with a remarkable increase in levels of Lactobacillus plantarum and associated changes in expression of antimicrobial and cuticle-related genes. PON1 expression directly decreased superoxide anion levels and altered bacterial colonization of the gut and its gene expression profile, highlighting the complex nature of the interaction between host genotype and gut microbiota. We speculate that the interaction between some genotypes and human diseases may be mediated by the presence of certain gut bacteria that can induce specific immune responses in the gut and other host tissues.
Symbiosis Gene Expression Intestinal Mucosa - metabolism Drosophila melanogaster - physiology Bacterial Load - genetics Humans Oxidative Stress - genetics Male Aryldialkylphosphatase - genetics Metagenome - genetics Animals Intestines - microbiology Superoxides - metabolism Female Lactobacillus - physiology

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