Publication Date:
2012-12-15
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780440/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780440/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connor, Tamara J -- Boyd, Dana -- Dorer, Marion S -- Isberg, Ralph R -- GM041883/GM/NIGMS NIH HHS/ -- R01 GM041883/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Dec 14;338(6113):1440-4. doi: 10.1126/science.1229556.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Molecular Microbiology and Microbiology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23239729" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bacterial Proteins/genetics
;
Bacterial Secretion Systems/*genetics
;
Cells, Cultured
;
Drosophila melanogaster/cytology
;
Flavoproteins/genetics
;
Genetic Testing/*methods
;
Host-Pathogen Interactions/*genetics
;
Humans
;
Legionella pneumophila/*genetics/*growth & development
;
Macrophages/microbiology
;
Mutagenesis, Insertional/*methods
;
RNA Interference
;
Sequence Deletion
;
Vacuoles/physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics