title: Aggravating genetic interactions allow a solution to redundancy in a bacterial pathogen.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Microbiology and Microbiology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: O'Connor
authors.forename: Dana
authors.initials: D
authors.lastname: Boyd
authors.forename: Marion S
authors.initials: MS
authors.lastname: Dorer
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D058947:Bacterial Secretion Systems / Q000235:genetics*; D002478:Cells, Cultured; D004331:Drosophila melanogaster / Q000166:cytology; D005420:Flavoproteins / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics* / Q000254:growth & development*; D008264:Macrophages / Q000382:microbiology; D016254:Mutagenesis, Insertional / Q000379:methods*; D034622:RNA Interference; D017384:Sequence Deletion; D014617:Vacuoles / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D005420:Flavoproteins; C084271:SdhA protein, Bacteria