Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 325 (5938): 340-343

Copyright © 2009 by the American Association for the Advancement of Science

Genome-Wide RNAi Screen Identifies Genes Involved in Intestinal Pathogenic Bacterial Infection

Shane J. F. Cronin,1,* Nadine T. Nehme,2,* Stefanie Limmer,2 Samuel Liegeois,2 J. Andrew Pospisilik,1 Daniel Schramek,1 Andreas Leibbrandt,1 Ricardo de Matos Simoes,3 Susanne Gruber,1 Urszula Puc,1 Ingo Ebersberger,3 Tamara Zoranovic,1 G. Gregory Neely,1 Arndt von Haeseler,3 Dominique Ferrandon,2,{dagger},{ddagger} Josef M. Penninger1,{dagger}

Abstract: Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.

1 IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria.
2 Equipe Fondation Recherche Médicale, UPR 9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire du CNRS, F-67084 Strasbourg, France.
3 Center for Integrative Bioinformatics (CIBIV), University of Vienna, Medical University of Vienna, University of Veterinary Medicine, A-1030 Vienna, Austria.

* These authors contributed equally to this work.

{dagger} This work is based on equal contributions from the laboratories of the last two authors.

{ddagger} To whom correspondence should be addressed. E-mail: d.ferrandon{at}

Subdued, a TMEM16 family Ca2+-activated Cl- channel in Drosophila melanogaster with an unexpected role in host defense.
X. M. Wong, S. Younger, C. J. Peters, Y. N. Jan, and L. Y. Jan (2013)
eLife Sci 2, e00862
   Abstract »    Full Text »    PDF »
ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells.
L. Niederreiter, T. M. J. Fritz, T. E. Adolph, A.-M. Krismer, F. A. Offner, M. Tschurtschenthaler, M. B. Flak, S. Hosomi, M. F. Tomczak, N. C. Kaneider, et al. (2013)
J. Exp. Med. 210, 2041-2056
   Abstract »    Full Text »    PDF »
Broad RNA Interference-Mediated Antiviral Immunity and Virus-Specific Inducible Responses in Drosophila.
C. Kemp, S. Mueller, A. Goto, V. Barbier, S. Paro, F. Bonnay, C. Dostert, L. Troxler, C. Hetru, C. Meignin, et al. (2013)
J. Immunol. 190, 650-658
   Abstract »    Full Text »    PDF »
Autocrine and paracrine unpaired signaling regulate intestinal stem cell maintenance and division.
D. Osman, N. Buchon, S. Chakrabarti, Y.-T. Huang, W.-C. Su, M. Poidevin, Y.-C. Tsai, and B. Lemaitre (2012)
J. Cell Sci. 125, 5944-5949
   Abstract »    Full Text »    PDF »
A Targeted In Vivo RNAi Screen Reveals Deubiquitinases as New Regulators of Notch Signaling.
J. Zhang, M. Liu, Y. Su, J. Du, and A. J. Zhu (2012)
g3 2, 1563-1575
   Abstract »    Full Text »    PDF »
On the Role of PDZ Domain-Encoding Genes in Drosophila Border Cell Migration.
G. Aranjuez, E. Kudlaty, M. S. Longworth, and J. A. McDonald (2012)
g3 2, 1379-1391
   Abstract »    Full Text »    PDF »
Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila.
J. B. Cordero, R. K. Stefanatos, A. Scopelliti, M. Vidal, and O. J. Sansom (2012)
EMBO J. 31, 3901-3917
   Abstract »    Full Text »    PDF »
Functional genomics in Drosophila models of human disease.
K.-F. Chen and D. C. Crowther (2012)
Briefings in Functional Genomics 11, 405-415
   Abstract »    Full Text »    PDF »
Drosophila as a model system to unravel the layers of innate immunity to infection.
I. Kounatidis and P. Ligoxygakis (2012)
Open Bio 2, 120075
   Abstract »    Full Text »    PDF »
Deconstructing host-pathogen interactions in Drosophila.
E. Bier and A. Guichard (2012)
Dis. Model. Mech. 5, 48-61
   Abstract »    Full Text »    PDF »
Controlling the Stem Cell Compartment and Regeneration In Vivo: The Role of Pluripotency Pathways.
K. Greenow and A. R. Clarke (2012)
Physiol Rev 92, 75-99
   Abstract »    Full Text »    PDF »
Nonautonomous regulation of Drosophila midgut stem cell proliferation by the insulin-signaling pathway.
N. H. Choi, E. Lucchetta, and B. Ohlstein (2011)
PNAS 108, 18702-18707
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model.
S. Limmer, S. Haller, E. Drenkard, J. Lee, S. Yu, C. Kocks, F. M. Ausubel, and D. Ferrandon (2011)
PNAS 108, 17378-17383
   Abstract »    Full Text »    PDF »
Pathogen and host factors are needed to provoke a systemic host response to gastrointestinal infection of Drosophila larvae by Candida albicans.
M. T. Glittenberg, I. Kounatidis, D. Christensen, M. Kostov, S. Kimber, I. Roberts, and P. Ligoxygakis (2011)
Dis. Model. Mech. 4, 515-525
   Abstract »    Full Text »    PDF »
Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells.
A. Amcheslavsky, N. Ito, J. Jiang, and Y. T. Ip (2011)
J. Cell Biol. 193, 695-710
   Abstract »    Full Text »    PDF »
Ral GTPase promotes asymmetric Notch activation in the Drosophila eye in response to Frizzled/PCP signaling by repressing ligand-independent receptor activation.
B. Cho and J. A. Fischer (2011)
Development 138, 1349-1359
   Abstract »    Full Text »    PDF »
Drosophila Ras/MAPK signalling regulates innate immune responses in immune and intestinal stem cells.
A. Ragab, T. Buechling, V. Gesellchen, K. Spirohn, A.-L. Boettcher, and M. Boutros (2011)
EMBO J. 30, 1123-1136
   Abstract »    Full Text »    PDF »
EGF signaling regulates the proliferation of intestinal stem cells in Drosophila.
B. Biteau and H. Jasper (2011)
Development 138, 1045-1055
   Abstract »    Full Text »    PDF »
Drosophila melanogaster as a model for human intestinal infection and pathology.
Y. Apidianakis and L. G. Rahme (2011)
Dis. Model. Mech. 4, 21-30
   Abstract »    Full Text »    PDF »
Models to study ancient host-pathogen interactions: lessons from Crete.
T. K. Means and A. Aballay (2011)
EMBO Rep. 12, 5-7
   Full Text »    PDF »
The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration.
R. L. Shaw, A. Kohlmaier, C. Polesello, C. Veelken, B. A. Edgar, and N. Tapon (2010)
Development 137, 4147-4158
   Abstract »    Full Text »    PDF »
Eye transformer is a negative regulator of Drosophila JAK/STAT signaling.
J. Kallio, H. Myllymaki, J. Gronholm, M. Armstrong, L.-M. Vanha-aho, L. Makinen, O. Silvennoinen, S. Valanne, and M. Ramet (2010)
FASEB J 24, 4467-4479
   Abstract »    Full Text »    PDF »
The 7a Accessory Protein of Severe Acute Respiratory Syndrome Coronavirus Acts as an RNA Silencing Suppressor.
S. Karjee, A. Minhas, V. Sood, S. S. Ponia, A. C. Banerjea, V. T. K. Chow, S. K. Mukherjee, and S. K. Lal (2010)
J. Virol. 84, 10395-10401
   Abstract »    Full Text »    PDF »
In vivo RNAi: Today and Tomorrow.
N. Perrimon, J.-Q. Ni, and L. Perkins (2010)
Cold Spring Harb Perspect Biol 2, a003640
   Abstract »    Full Text »    PDF »
Paracrine Unpaired Signaling through the JAK/STAT Pathway Controls Self-renewal and Lineage Differentiation of Drosophila Intestinal Stem Cells.
G. Lin, N. Xu, and R. Xi (2010)
J Mol Cell Biol 2, 37-49
   Abstract »    Full Text »    PDF »
RNAi screens to identify components of gene networks that modulate aging in Caenorhabditis elegans.
Z. Ni and S. S. Lee (2010)
Briefings in Functional Genomics
   Abstract »    Full Text »    PDF »
Synergy between bacterial infection and genetic predisposition in intestinal dysplasia.
Y. Apidianakis, C. Pitsouli, N. Perrimon, and L. Rahme (2009)
PNAS 106, 20883-20888
   Abstract »    Full Text »    PDF »
Bacterial-modulated host immunity and stem cell activation for gut homeostasis.
W.-J. Lee (2009)
Genes & Dev. 23, 2260-2265
   Abstract »    Full Text »    PDF »
Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila.
N. Buchon, N. A. Broderick, S. Chakrabarti, and B. Lemaitre (2009)
Genes & Dev. 23, 2333-2344
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882