Affiliation:
1. Department of BioSciences, Rice University, Houston, Texas, USA
Abstract
Despite intense research effort from scientists and the advent of the molecular age of biomedical research, many of the mechanisms that underlie pathogenesis are still understood poorly, if at all. The opportunistic human pathogen
Pseudomonas aeruginosa
causes a variety of soft tissue infections and is responsible for over 50,000 hospital-acquired infections per year. In addition,
P. aeruginosa
exhibits a striking degree of innate and acquired antimicrobial resistance, complicating treatment. It is increasingly important to understand
P. aeruginosa
virulence. In an effort to gain this information in an unbiased fashion, we used a high-throughput phenotypic screen to identify small molecules that disrupted bacterial pathogenesis and increased host survival using the model nematode
Caenorhabditis elegans
. This method led to the unexpected discovery that addition of a modified nucleotide, 5-fluorouridine, disrupted bacterial RNA metabolism and inhibited synthesis of pyoverdine, a critical toxin. Our results demonstrate that this compound specifically functions as an antivirulent.
Funder
HHS | NIH | National Institute of Allergy and Infectious Diseases
Cancer Prevention and Research Institute of Texas
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
51 articles.
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