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Science. 2012 Dec 14;338(6113):1440-4. doi: 10.1126/science.1229556.

Aggravating genetic interactions allow a solution to redundancy in a bacterial pathogen.

Author information

1
Howard Hughes Medical Institute and Department of Molecular Microbiology and Microbiology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.

Abstract

Interactions between hosts and pathogens are complex, so understanding the events that govern these interactions requires the analysis of molecular mechanisms operating in both organisms. Many pathogens use multiple strategies to target a single event in the disease process, confounding the identification of the important determinants of virulence. We developed a genetic screening strategy called insertional mutagenesis and depletion (iMAD) that combines bacterial mutagenesis and RNA interference, to systematically dissect the interplay between a pathogen and its host. We used this technique to resolve the network of proteins secreted by the bacterium Legionella pneumophila to promote intracellular growth, a critical determinant of pathogenicity of this organism. This strategy is broadly applicable, allowing the dissection of any interface between two organisms involving numerous interactions.

PMID:
23239729
PMCID:
PMC3780440
DOI:
10.1126/science.1229556
[Indexed for MEDLINE]
Free PMC Article

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