Innovative Therapies

RNA & Infection

Host-pathogen interactions

Bacterial Pathogens

Non-coding RNAs

MicroRNAs

High-throughput/high-content Screening

Overview

Although the vast majority of bacteria are innocuous or even beneficial to mammalian hosts, infections by pathogenic bacteria account for a variety of diseases that, despite the existing antibiotics, continue to threaten public health worldwide.

Bacterial infections are characterized by a complex interplay between pathogens and host cells, leading to alterations of multiple host cell functions. However, the impact of bacterial infection on host RNA metabolism, including non-coding RNA (ncRNA) expression and function, as well as the reciprocal impact of host RNA metabolism in the life cycle of bacterial pathogens remain largely unexplored. A proper RNA metabolism is essential to a number host cell functions and therefore it is not surprising that it contributes to a proper defense against infection, and that, on the other hand, pathogens have evolved sophisticated mechanisms to subvert these pathways to their own benefit.

The main goal of the laboratory is to identify host ncRNAs (specifically, microRNAs and long ncRNAs) that regulate and/or are regulated during infection by human bacterial pathogens (e.g. Salmonella Typhimurium, Shigella flexneri, Campylobacter jejuni and Staphylococcus aureus) and to characterize the molecular mechanisms underlying their function. To achieve this goal we are applying systematic approaches, including gain- and loss-of-function screenings using genome-wide microRNA libraries and ncRNA profiling by RNA-seq.

The identification of these ncRNAs will be instrumental to the development of novel therapeutic approaches against pathogenic bacteria, either through the modulation of selected ncRNAs, or of their targets.

Featured Articles

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Information about journal articles, updated at 01-12-2024, from platform CIÊNCIAVITAE.

Microscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature

Rodrigues Lopes, Inês; Laura Maria Alcantara; Ricardo Silva; Jérôme JOSSE; Elena Pedrero Vega; Ana Marina Cabrerizo; Melanie Bonhomme; et al, 2022. Nature Communications. 1. 13. 2022. 10.1038/s41467-022-34790-9 . Nature Communications

Reprogramming of microRNA expression via E2F1 downregulation promotes Salmonella infection both in infected and bystander cells

Carmen Aguilar; Susana Costa; Claire Maudet; R. P. Vivek-Ananth; Sara Zaldívar-López; Juan J. Garrido; Areejit Samal; Miguel Mano; Ana Eulalio, 2021. Nature Communications. 2021. 10.1038/s41467-021-23593-z . Nature Communications

Dysregulated endolysosomal trafficking in cells arrested in the G1 phase of the host cell cycle impairs Salmonella vacuolar replication

Lisowski, Clivia; Dias, Jane; Costa, Susana; Silva, Ricardo Jorge; Mano, Miguel; Eulalio, Ana, 2021. Autophagy. 1 - 16. 2021. 10.1080/15548627.2021.1999561 . published Autophagy

Functional screenings reveal different requirements for host microRNAs in Salmonella and Shigella infection

Aguilar, C.; Cruz, A.R.; Rodrigues Lopes, I.; Maudet, C.; Sunkavalli, U.; Silva, R.J.; Sharan, M.; et al, 2020. Nature Microbiology. 192 - 205. 1. 5. 2020. 10.1038/s41564-019-0614-3 . Nature Microbiology

Stress-induced host membrane remodeling protects from infection by non-motile bacterial pathogens

Tawk, C.; Nigro, G.; Rodrigues Lopes, I.; Aguilar, C.; Lisowski, C.; Mano, M.; Sansonetti, P.; Vogel, J.; Eulalio, A., 2018. The EMBO Journal. 23. 37. 2018. 10.15252/embj.201798529 . The EMBO Journal


Publications

Show less

Information about journal articles, updated at 01-12-2024, from platform CIÊNCIAVITAE.

Microscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature

Rodrigues Lopes, Inês; Laura Maria Alcantara; Ricardo Silva; Jérôme JOSSE; Elena Pedrero Vega; Ana Marina Cabrerizo; Melanie Bonhomme; et al, 2022. Nature Communications. 1. 13. 2022. 10.1038/s41467-022-34790-9 . Nature Communications

The induction of natural competence adapts staphylococcal metabolism to infection

Mar Cordero; Julia García-Fernández; Ivan C. Acosta; Ana Yepes; Jose Avendano-Ortiz; Clivia Lisowski; Babett Oesterreicht; et al, 2022. Nature Communications. 1. 13. 2022. 10.1038/s41467-022-29206-7 . Nature Communications

Dysregulated endolysosomal trafficking in cells arrested in the G1 phase of the host cell cycle impairs Salmonella vacuolar replication

Lisowski, Clivia; Dias, Jane; Costa, Susana; Silva, Ricardo Jorge; Mano, Miguel; Eulalio, Ana, 2021. Autophagy. 1 - 16. 2021. 10.1080/15548627.2021.1999561 . published Autophagy

Reprogramming of microRNA expression via E2F1 downregulation promotes Salmonella infection both in infected and bystander cells

Carmen Aguilar; Susana Costa; Claire Maudet; R. P. Vivek-Ananth; Sara Zaldívar-López; Juan J. Garrido; Areejit Samal; Miguel Mano; Ana Eulalio, 2021. Nature Communications. 2021. 10.1038/s41467-021-23593-z . Nature Communications

Functional screenings reveal different requirements for host microRNAs in Salmonella and Shigella infection

Aguilar, C.; Cruz, A.R.; Rodrigues Lopes, I.; Maudet, C.; Sunkavalli, U.; Silva, R.J.; Sharan, M.; et al, 2020. Nature Microbiology. 192 - 205. 1. 5. 2020. 10.1038/s41564-019-0614-3 . Nature Microbiology

MicroRNAs at the Host–Bacteria Interface: Host Defense or Bacterial Offense

Aguilar, C.; Mano, M.; Eulalio, A., 2019. Trends in Microbiology. 206 - 218. 3. 27. 2019. 10.1016/j.tim.2018.10.011 . Trends in Microbiology

Multifaceted roles of microRNAs in host-bacterial pathogen interaction

Aguilar, C.; Mano, M.; Eulalio, A., 2019. Microbiology Spectrum. 3. 7. 2019. 10.1128/microbiolspec.BAI-0002-2019 . Microbiology Spectrum

Shedding light on microRNA function via microscopy-based screening

Rodrigues Lopes, I.; Silva, R.J.; Caramelo, I.; Mano, M.; Eulalio, A., 2019. Methods. 2019. 10.1016/j.ymeth.2018.09.011 . Methods

Stress-induced host membrane remodeling protects from infection by non-motile bacterial pathogens

Tawk, C.; Nigro, G.; Rodrigues Lopes, I.; Aguilar, C.; Lisowski, C.; Mano, M.; Sansonetti, P.; Vogel, J.; Eulalio, A., 2018. The EMBO Journal. 23. 37. 2018. 10.15252/embj.201798529 . The EMBO Journal

Chlamydia preserves the mitochondrial network necessary for replication via microRNA-dependent inhibition of fission

Chowdhury, S.R.; Reimer, A.; Sharan, M.; Kozjak-Pavlovic, V.; Eulalio, A.; Prusty, B.K.; Fraunholz, M.; Karunakaran, K.; Rudel, T., 2017. Journal of Cell Biology. 1071 - 1089. 4. 216. 2017. 10.1083/jcb.201608063 . Journal of Cell Biology

APRICOT: An integrated computational pipeline for the sequence-based identification and characterization of RNA-binding proteins

Sharan, M.; Forstner, K.U.; Eulalio, A.; Vogel, J., 2017. Nucleic Acids Research. e96 - e96. 11. 45. 2017. 10.1093/nar/gkx137 . Nucleic Acids Research

A systematic analysis of the RNA-targeting potential of secreted bacterial effector proteins

Tawk, C.; Sharan, M.; Eulalio, A.; Vogel, J., 2017. Scientific Reports. 1. 7. 2017. 10.1038/s41598-017-09527-0 . Scientific Reports

Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia

Sunkavalli, U.; Aguilar, C.; Silva, R.J.; Sharan, M.; Cruz, A.R.; Tawk, C.; Maudet, C.; Mano, M.; Eulalio, A., 2017. PLoS Pathogens. 4. 13. 2017. 10.1371/journal.ppat.1006327 . PLoS Pathogens

MicroRNA Screening and the Quest for Biologically Relevant Targets

Eulalio, A.; Mano, M., 2015. Journal of Biomolecular Screening. 1003 - 1017. 8. 20. 2015. 10.1177/1087057115578837 . Journal of Biomolecular Screening

Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection

Maudet, C.; Mano, M.; Sunkavalli, U.; Sharan, M.; Giacca, M.; Förstner, K.U.; Eulalio, A., 2014. Nature Communications. 5. 2014. 10.1038/ncomms5718 . Nature Communications

MicroRNAs in the interaction between host and bacterial pathogens

Maudet, C.; Mano, M.; Eulalio, A., 2014. FEBS Letters. 4140 - 4147. 22. 588. 2014. 10.1016/j.febslet.2014.08.002 . FEBS Letters

The interactions of GW182 proteins with PABP and deadenylases are required for both translational repression and degradation of miRNA targets

Huntzinger, E.; Kuzuoglu-Öztürk, D.; Braun, J.E.; Eulalio, A.; Wohlbold, L.; Izaurralde, E., 2013. Nucleic Acids Research. 978 - 994. 2. 41. 2013. 10.1093/nar/gks1078 . Nucleic Acids Research

The mammalian microRNA response to bacterial infections

Eulalio, A.; Schulte, L.N.; Voge, J., 2012. RNA Biology. 742 - 750. 6. 9. 2012. 10.4161/rna.20018 . RNA Biology

Functional screening identifies miRNAs inducing cardiac regeneration

Eulalio, A.; Mano, M.; Ferro, M.D.; Zentilin, L.; Sinagra, G.; Zacchigna, S.; Giacca, M., 2012. Nature. 376 - 381. 7429. 492. 2012. 10.1038/nature11739 . Nature

Terminal differentiation of cardiac and skeletal myocytes induces permissivity to AAV transduction by relieving inhibition imposed by DNA damage response proteins

Lovric, J.; Mano, M.; Zentilin, L.; Eulalio, A.; Zacchigna, S.; Giacca, M., 2012. Molecular Therapy. 2087 - 2097. 11. 20. 2012. 10.1038/mt.2012.144 . Molecular Therapy

Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family

Schulte, L.N.; Eulalio, A.; Mollenkopf, H.-J.; Reinhardt, R.; Vogel, J., 2011. EMBO Journal. 1977 - 1989. 10. 30. 2011. 10.1038/emboj.2011.94 . EMBO Journal

A candidate approach implicates the secreted Salmonella effector protein SpvB in P-body disassembly

Eulalio, A.; Fröhlich, K.S.; Mano, M.; Giacca, M.; Vogel, J., 2011. PLoS ONE. 3. 6. 2011. 10.1371/journal.pone.0017296 . PLoS ONE

Analysis of a to I editing of miRNA in macrophages exposed to salmonella

Heale, B.S.E.; Eulalio, A.; Schulte, L.; Vogel, J.; O'Connell, M.A., 2010. RNA Biology. 621 - 627. 5. 7. 2010. 10.4161.rna.7.5.13269 . RNA Biology

Deadenylation is a widespread effect of miRNA regulation

Eulalio, A.; Huntzinger, E.; Nishihara, T.; Rehwinkel, J.; Fauser, M.; Izaurralde, E., 2009. RNA. 21 - 32. 1. 15. 2009. 10.1261/rna.1399509 . RNA

The GW182 protein family in animal cells: New insights into domains required for miRNA-mediated gene silencing

Eulalio, A.; Tritschler, F.; Izaurralde, E., 2009. RNA. 1433 - 1442. 8. 15. 2009. 10.1261/rna.1703809 . RNA

A C-terminal silencing domain in GW182 is essential for miRNA function

Eulalio, A.; Helms, S.; Fritzsch, C.; Fauser, M.; Izaurralde, E., 2009. RNA. 1067 - 1077. 6. 15. 2009. 10.1261/rna.1605509 . RNA

The RRM domain in GW182 proteins contributes to miRNA-mediated gene silencing

Eulalio, A.; Tritschler, F.; Budie;ttner, R.; Weichenrieder, O.; Izaurralde, E.; Truffault, V., 2009. Nucleic Acids Research. 2974 - 2983. 9. 37. 2009. 10.1093/nar/gkp173 . Nucleic Acids Research

Structural Basis for the Mutually Exclusive Anchoring of P Body Components EDC3 and Tral to the DEAD Box Protein DDX6/Me31B

Tritschler, F.; Braun, J.E.; Eulalio, A.; Truffault, V.; Izaurralde, E.; Weichenrieder, O., 2009. Molecular Cell. 661 - 668. 5. 33. 2009. 10.1016/j.molcel.2009.02.014 . Molecular Cell

GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay

Eulalio, A.; Huntzinger, E.; Izaurralde, E., 2008. Nature Structural and Molecular Biology. 346 - 353. 4. 15. 2008. 10.1038/nsmb.1405 . Nature Structural and Molecular Biology

Getting to the Root of miRNA-Mediated Gene Silencing

Eulalio, A.; Huntzinger, E.; Izaurralde, E., 2008. Cell. 9 - 14. 1. 132. 2008. 10.1016/j.cell.2007.12.024 . Cell

Similar modes of interaction enable trailer hitch and EDC3 to associate with DCP1 and Me31B in distinct protein complexes

Tritschler, F.; Eulalio, A.; Helms, S.; Schmidt, S.; Coles, M.; Weichenrieder, O.; Izaurralde, E.; Truffault, V., 2008. Molecular and Cellular Biology. 6695 - 6708. 21. 28. 2008. 10.1128/MCB.00759-08 . Molecular and Cellular Biology

The C-terminal region of Ge-1 presents conserved structural features required for P-body localization

Jinek, M.; Eulalio, A.; Lingel, A.; Helms, S.; Conti, E.; Izaurralde, E., 2008. RNA. 1991 - 1998. 10. 14. 2008. 10.1261/rna.1222908 . RNA

African swine fever virus p10 protein exhibits nuclear import capacity and accumulates in the nucleus during viral infection

Nunes-Correia, I.; Rodríguez, J.M.; Eulálio, A.; Carvalho, A.L.; Citovsky, V.; Simões, S.; Faro, C.; Salas, M.L.; Pedroso de Lima, M.C., 2008. Veterinary Microbiology. 47 - 59. 1-2. 130. 2008. 10.1016/j.vetmic.2007.12.010 . Veterinary Microbiology

African swine fever virus p37 structural protein is localized in nuclear foci containing the viral DNA at early post-infection times

Eulálio, A.; Nunes-Correia, I.; Salas, J.; Salas, M.L.; Simões, S.; Pedroso de Lima, M.C., 2007. Virus Research. 18 - 27. 1-2. 130. 2007. 10.1016/j.virusres.2007.05.009 . Virus Research

A divergent Sm fold in EDC3 proteins mediates DCP1 binding and P-body targeting

Tritschler, F.; Eulalio, A.; Truffault, V.; Hartmann, M.D.; Helms, S.; Schmidt, S.; Coles, M.; Izaurralde, E.; Weichenrieder, O., 2007. Molecular and Cellular Biology. 8600 - 8611. 24. 27. 2007. 10.1128/MCB.01506-07 . Molecular and Cellular Biology

Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing

Eulalio, A.; Rehwinkel, J.; Stricker, M.; Huntzinger, E.; Yang, S.-F.; Doerks, T.; Dorner, S.; et al, 2007. Genes and Development. 2558 - 2570. 20. 21. 2007. 10.1101/gad.443107 . Genes and Development

Delving into the diversity of silencing pathways. Symposium on MicroRNAs and siRNAs: Biological Functions and Mechanisms

Dorner, S.; Eulalio, A.; Huntzinger, E.; Izaurralde, E., 2007. EMBO Reports. 723 - 729. 8. 8. 2007. 10.1038/sj.embor.7401015 . EMBO Reports

P bodies: At the crossroads of post-transcriptional pathways

Eulalio, A.; Behm-Ansmant, I.; Izaurralde, E., 2007. Nature Reviews Molecular Cell Biology. 9 - 22. 1. 8. 2007. 10.1038/nrm2080 . Nature Reviews Molecular Cell Biology

P-body formation is a consequence, not the cause, of RNA-mediated gene silencing

Eulalio, A.; Behm-Ansmant, I.; Schweizer, D.; Izaurralde, E., 2007. Molecular and Cellular Biology. 3970 - 3981. 11. 27. 2007. 10.1128/MCB.00128-07 . Molecular and Cellular Biology

Nuclear export of African swine fever virus p37 protein occurs through two distinct pathways and is mediated by three independent signals

Eulálio, A.; Nunes-Correia, I.; Carvalho, A.L.; Faro, C.; Citovsky, V.; Salas, J.; Salas, M.L.; Simões, S.; Pedroso De Lima, M.C., 2006. Journal of Virology. 1393 - 1404. 3. 80. 2006. 10.1128/JVI.80.3.1393-1404.2006 . Journal of Virology

Caveolae as an additional route for influenza virus endocytosis in MDCK cells

Nunes-Correia, I.; Eulálio, A.; Nir, S.; Pedroso De Lima, M.C., 2004. Cellular and Molecular Biology Letters. 47 - 60. 1. 9. 2004. Cellular and Molecular Biology Letters

Two African swine fever virus proteins derived from a common precursor exhibit different nucleocytoplasmic transport activities

Eulálio, A.; Nunes-Correia, I.; Carvalho, A.L.; Faro, C.; Citovsky, V.; Simões, S.; De Lima, M.C.P., 2004. Journal of Virology. 9731 - 9739. 18. 78. 2004. 10.1128/JVI.78.18.9731-9739.2004 . Journal of Virology

Fluorescent probes for monitoring virus fusion kinetics: Comparative evaluation of reliability

Nunes-Correia, I.; Eulálio, A.; Nir, S.; Düzgünes, N.; Ramalho-Santos, J.; Pedroso De Lima, M.C., 2002. Biochimica et Biophysica Acta - Biomembranes. 65 - 75. 1. 1561. 2002. 10.1016/S0005-2736(01)00457-6 . Biochimica et Biophysica Acta - Biomembranes

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