Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2013 (arch)     Display Documents



  history
ID: 688578.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2013 (arch)
Integration of chemical and RNAi multiparametric profiles identifies triggers of intracellular mycobacterial killing.
Authors:Sundaramurthy, Varadharajan; Barsacchi, Rico; Samusik, Nikolay; Marsico, Giovanni; Gilleron, Jerome; Kalaidzidis, Inna; Meyenhofer, Felix; Bickle, Marc; Kalaidzidis, Yannis; Zerial, Marino
Date of Publication (YYYY-MM-DD):2013
Title of Journal:Cell Host & Microbe
Volume:13
Issue / Number:2
Start Page:129
End Page:142
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Pharmacological modulators of host-microbial interactions can in principle be identified using high-content screens. However, a severe limitation of this approach is the lack of insights into the mode of action of compounds selected during the primary screen. To overcome this problem, we developed a combined experimental and computational approach. We designed a quantitative multiparametric image-based assay to measure intracellular mycobacteria in primary human macrophages, screened a chemical library containing FDA-approved drugs, and validated three compounds for intracellular killing of M. tuberculosis. By integrating the multiparametric profiles of the chemicals with those of siRNAs from a genome-wide survey on endocytosis, we predicted and experimentally verified that two compounds modulate autophagy, whereas the third accelerates endosomal progression. Our findings demonstrate the value of integrating small molecules and genetic screens for identifying cellular mechanisms modulated by chemicals. Furthermore, selective pharmacological modulation of host trafficking pathways can be applied to intracellular pathogens beyond mycobacteria.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Lib
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:5321
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.