Microbiology, Virology & Host Pathogen Interaction
- Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing
- 1Department of Biological Sciences, Eck Institute for Global Health, Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN, USA
- ↵*Corresponding author. Tel: +1 574 631 3734; Fax: +1 574 631 7413; E‐mail: schorey.1{at}nd.edu
Extracellular vesicles carry microbial components and have roles during host defence. EVs released from M. tuberculosis‐infected macrophages activate the cytosolic RNA sensing pathway, and potentiate antibiotic treatment in an infection model.
Synopsis
Extracellular vesicles carry microbial components and have roles during host defence. EVs released from M. tuberculosis‐infected macrophages activate the cytosolic RNA sensing pathway, and potentiate antibiotic treatment in an infection model.
EVs from M.tb‐infected macrophages stimulate RIG‐I/MAVS/TBK1/IRF3 RNA sensing pathways.
EVs promote LC3‐associated phagosome maturation in M.tb‐infected macrophages.
EVs inhibit M.tb survival in macrophages via a MAVS‐dependent pathway.
EVs significantly increase the efficacy of the antibiotic moxifloxacin in M.tb infected mice.
EMBO Reports (2019) 20: e46613
- Received June 19, 2018.
- Revision received December 14, 2018.
- Accepted December 19, 2018.
- © 2019 The Authors
- Mimicry by a viral RHIM
- 1Instituto Regional de Investigación Científica Aplicada (IRICA), University of Castile‐La Mancha, Ciudad Real, Spain
- 2Department of Chemistry, Columbia University, New York, NY, USA
- 3Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
- 4Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA
↵† These authors contributed equally to this work
Functional amyloids have recently attracted much attention due to their involvement in signalling pathways, with hybrid amyloid formation showcasing a key role in necroptosis. In this issue of EMBO Reports, Sunde and colleagues [1] unveil that hybrid amyloids are central to necroptosis more broadly, uncovering the amyloidal nature of viral‐induced necrosome assemblies. They also prove that the mechanism by which murine cytomegalovirus unleashes necroptosis also relies on hybrid amyloid assembly by viral proteins, akin to that used by host cells. This study presents a way to selectively inhibit necroptosis in which amyloid assembly can be exploited further as a potential therapeutic target.
See also: CLL Pham et al (February 2019)
A report in this issue describes that the murine herpesvirus cytomegalovirus triggers necroptosis via hybrid amyloid assemblies by viral proteins similar to those used by host cells, suggesting means to selectively inhibit virus‐induced necroptosis.
EMBO Reports (2019) 20: e47433
- © 2019 The Authors
- Serendipita indica E5′NT modulates extracellular nucleotide levels in the plant apoplast and affects fungal colonization
- Shadab Nizam1,2,
- Xiaoyu Qiang1,2,
- Stephan Wawra2,
- Robin Nostadt1,
- Felix Getzke2,
- Florian Schwanke2,
- Ingo Dreyer3,
- Gregor Langen2 and
- Alga Zuccaro (azuccaro{at}uni-koeln.de)*,1,2
- 1Max Planck Institute for Terrestrial Microbiology, Marburg, Germany
- 2Botanical Institute, Cluster of Excellence on Plant Sciences (CEPLAS), Cologne Biocenter, University of Cologne, Cologne, Germany
- 3Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile
- ↵*Corresponding author. Tel: +49 2214 707170; E‐mail: azuccaro{at}uni-koeln.de
The beneficial fungal root endophyte Serendipita indica alters extracellular nucleotide levels and plant responses to biotic stresses.
Synopsis
The beneficial fungal root endophyte Serendipita indica alters extracellular nucleotide levels and plant responses to biotic stresses.
Extracellular ATP accumulates in the plant apoplast during root colonization by S. indica at early symbiotic stages.
Perception of extracellular nucleotides, such as eATP, is important in plant‐fungus interactions.
S. indica secrets E5′NT, an enzymatically active ecto‐5′‐nucleotidase that can modify apoplastic metabolites and promotes fungal accommodation.
EMBO Reports (2019) 20: e47430
- Received November 20, 2018.
- Revision received December 13, 2018.
- Accepted December 14, 2018.
- © 2019 The Authors. Published under the terms of the CC BY 4.0 license.
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- From conjugation to T4S systems in Gram‐negative bacteria: a mechanistic biology perspective
- ↵*Corresponding author. Tel: +44 207 631 6833; E‐mail: g.waksman{at}mail.cryst.bbk.ac.uk
In Gram‐negative bacteria conjugation is mediated by a large membrane‐embedded nanomachine of the type IV secretion (T4S) system. This review highlights recent research on conjugation and T4S systems, and provides a comprehensive structural and mechanistic overview.
EMBO Reports (2019) 20: e47012
- Received September 5, 2018.
- Revision received October 31, 2018.
- Accepted November 27, 2018.
- © 2019 The Author. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Bacterial FtsZ protein forms phase‐separated condensates with its nucleoid‐associated inhibitor SlmA
- Begoña Monterroso (monterroso{at}cib.csic.es)*,1,†,
- Silvia Zorrilla (silvia{at}cib.csic.es)*,1,†,
- Marta Sobrinos‐Sanguino1,
- Miguel A Robles‐Ramos1,
- Marina López‐Álvarez1,
- William Margolin2,
- Christine D Keating3 and
- Germán Rivas (grivas{at}cib.csic.es)*,1
- 1Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- 2Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas, Houston, TX, USA
- 3Department of Chemistry, Pennsylvania State University, University Park, PA, USA
- ↵*
Corresponding author. Tel: +34 918373112; E‐mail: monterroso{at}cib.csic.es
Corresponding author. Tel: +34 918373112; E‐mail: silvia{at}cib.csic.es
Corresponding author. Tel: +34 918373112; E‐mail: grivas{at}cib.csic.es
↵† These authors contributed equally to this work
Elements of the bacterial cell division machinery assemble into condensates by liquid‐liquid phase separation in cell‐like crowded conditions. This suggests that phase‐separated condensation may also help to organize intracellular space in bacteria.
Synopsis
Elements of the bacterial cell division machinery assemble into condensates by liquid‐liquid phase separation in cell‐like crowded conditions. This suggests that phase‐separated condensation may also help to organize intracellular space in bacteria.
The essential bacterial cell division protein FtsZ forms phase‐separated condensates in the presence of nucleoprotein complexes organized by the FtsZ spatial regulator SlmA.
The condensates are dynamic and disband upon GTP‐dependent reversible formation of FtsZ fibers whose lifetimes are significantly shortened by SlmA.
Condensates are observed in cell‐like crowding conditions in solution and inside phase‐separated systems encircled by a lipid membrane.
Phase‐separated FtsZ condensates may constitute a novel element of spatiotemporal organization of essential bacterial cell cycle processes.
EMBO Reports (2019) 20: e45946
- Received February 12, 2018.
- Revision received October 29, 2018.
- Accepted November 7, 2018.
- © 2018 The Authors
- Viral M45 and necroptosis‐associated proteins form heteromeric amyloid assemblies
- Chi LL Pham1,
- Nirukshan Shanmugam1,
- Merryn Strange1,
- Ailis O'Carroll2,
- James WP Brown2,
- Emma Sierecki2,
- Yann Gambin2,
- Megan Steain3 and
- Margaret Sunde (margaret.sunde{at}sydney.edu.au)*,1
- 1Discipline of Pharmacology, School of Medical Sciences, Faculty of Medicine and Health and Sydney Nano, University of Sydney, Sydney, NSW, Australia
- 2EMBL Australia Node in Single Molecule Sciences, School of Medical Science, University of New South Wales, Sydney, NSW, Australia
- 3Infectious Diseases and Immunology, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- ↵*Corresponding author. Tel: +612 9351 6955; E‐mail: margaret.sunde{at}sydney.edu.au
The murine cytomegalovirus protein M45 forms heteromeric amyloid fibrils with RIPK1, ZBP1 and RIPK3 through its RIP homotypic interaction motif. The sequestration of RHIM proteins in M45‐contaning fibrils might explain its ability to inhibit necroptosis.
Synopsis
The murine cytomegalovirus protein M45 forms heteromeric amyloid fibrils with RIPK1, ZBP1 and RIPK3 through its RIP homotypic interaction motif. The sequestration of RHIM proteins in M45‐contaning fibrils might explain its ability to inhibit necroptosis.
The viral M45 protein forms functional amyloid fibrils.
M45 forms heteromeric amyloid fibrils with host RHIM proteins.
M45 preferentially interacts with ZBP1 and RIPK3 over RIPK1.
EMBO Reports (2019) 20: e46518
- Received May 31, 2018.
- Revision received November 5, 2018.
- Accepted November 7, 2018.
- © 2018 The Authors
- You can't always sequence your way out of a tight spotNext‐generation sequencing holds great promise for pathogen detection, but the devil is in the details
Next‐generation sequencing holds great promise for pathogen detection, but the devil is in the details
While DNA sequencing is increasingly being used as a diagnostic tool, targeted assays, culture and other isolation techniques remain a critical component in effective diagnostic workflows.
- © 2018 The Authors
- ADP‐heptose is a newly identified pathogen‐associated molecular pattern of Shigella flexneri
- Diego García‐Weber1,2,3,†,
- Anne‐Sophie Dangeard1,2,3,†,
- Johan Cornil4,5,
- Linda Thai4,5,
- Héloïse Rytter1,
- Alla Zamyatina6,
- Laurence A Mulard4,5 and
- Cécile Arrieumerlou (cecile.arrieumerlou{at}inserm.fr)*,1
- 1INSERM, U1016, Institut Cochin, Paris, France
- 2CNRS, UMR8104, Paris, France
- 3Université Paris Descartes, Sorbonne Paris Cité, Paris, France
- 4Chemistry of Biomolecules Laboratory, Institut Pasteur, Paris Cedex 15, France
- 5CNRS UMR3523, Institut Pasteur, Paris, France
- 6Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria
- ↵*Corresponding author. Tel: +33 1 40516411; E‐mail: cecile.arrieumerlou{at}inserm.fr
↵† These authors contributed equally to this work
ADP‐heptose is a newly identified pathogen‐associated molecular pattern of Shigella flexneri. Unlike βHBP, ADP‐heptose triggers rapid ALPK1‐dependent TIFA oligomerization leading to subsequent inflammatory cytokine production.
Synopsis
ADP‐heptose is a newly identified pathogen‐associated molecular pattern of Shigella flexneri. Unlike βHBP, ADP‐heptose triggers rapid ALPK1‐dependent TIFA oligomerization leading to subsequent inflammatory cytokine production.
During Shigella flexneri infection, recognition of bacterial ADP‐heptose elicits rapid oligomerization of TIFA and the production of inflammatory cytokines.
ALPK1 silencing abrogates ADP‐heptose‐induced TIFA oligomerization and cytokine production.
EMBO Reports (2018) 19: e46943
- Received August 23, 2018.
- Revision received October 26, 2018.
- Accepted October 29, 2018.
- © 2018 The Authors
- Bacterial infections and cancer
- 1Oncode Institute and Department of Cell and Chemical Biology, Leiden University Medical Center LUMC, Leiden, The Netherlands
- ↵*Corresponding author. Tel: +31 70 5168722; E‐mail: j.j.c.neefjes{at}lumc.nl
Many bacteria directly manipulate their host cell in various phases of their infection cycle. This review describes how bacterial surface moieties, protein toxins and effector proteins interfere with essential host cell signalling pathways, thereby promoting cancer formation.
EMBO Reports (2018) 19: e46632
- Received June 25, 2018.
- Revision received August 10, 2018.
- Accepted September 24, 2018.
- © 2018 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- The fungal ligand chitin directly binds TLR2 and triggers inflammation dependent on oligomer size
- Katharina Fuchs1,†,
- Yamel Cardona Gloria1,†,
- Olaf‐Oliver Wolz1,
- Franziska Herster1,
- Lokesh Sharma2,
- Carly A Dillen3,
- Christoph Täumer4,
- Sabine Dickhöfer1,
- Zsofia Bittner1,
- Truong‐Minh Dang1,
- Anurag Singh5,
- Daniel Haischer6,
- Maria A Schlöffel6,
- Kirsten J Koymans7,
- Tharmila Sanmuganantham1,
- Milena Krach1,
- Thierry Roger8,
- Didier Le Roy8,
- Nadine A Schilling9,
- Felix Frauhammer10,11,
- Lloyd S Miller3,
- Thorsten Nürnberger6,
- Salomé LeibundGut‐Landmann12,
- Andrea A Gust6,
- Boris Macek4,
- Martin Frank13,
- Cécile Gouttefangeas1,
- Charles S Dela Cruz2,
- Dominik Hartl5,14 and
- Alexander NR Weber (alexander.weber{at}uni-tuebingen.de)*,1
- 1Department of Immunology, University of Tübingen, Tübingen, Germany
- 2Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Department of Microbial Pathogenesis, Center for Pulmonary Infection Research and Infection (CPIRT), New Haven, CT, USA
- 3Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- 4Department of Quantitative Proteomics and Proteome Center, University of Tübingen, Tübingen, Germany
- 5University Children's Hospital and Interdisciplinary Center for Infectious Diseases, University of Tübingen, Tübingen, Germany
- 6Center for Plant Molecular Biology, University of Tübingen, Tübingen, Germany
- 7Department of Medical Microbiology, University Medical Center Utrecht, CX Utrecht, The Netherlands
- 8Infectious Diseases Service, Lausanne University Hospital, Epalinges, Switzerland
- 9Institute of Organic Chemistry, University of Tübingen, Tübingen, Germany
- 10Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany
- 11Department of Dermatology, Heidelberg University, Heidelberg, Germany
- 12Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland
- 13Biognos AB, Göteborg, Sweden
- 14Roche Pharma Research & Early Development (pRED), Immunology, Inflammation and Infectious Diseases (I3) Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland
- ↵*Corresponding author. Tel: +49 7071 29 87623; Fax: +49 7071 29 4579; E‐mail: alexander.weber{at}uni-tuebingen.de
↵† These authors contributed equally to this work
Chitin, a polysaccharide linked to fungal infection and allergic asthma, directly binds to the innate immune receptor TLR2 and triggers inflammation dependent on oligomer size. Blocking the chitin‐TLR2 interaction effectively prevents chitin‐mediated inflammation.
Synopsis
Chitin, a polysaccharide linked to fungal infection and allergic asthma, directly binds to the innate immune receptor TLR2 and triggers inflammation dependent on oligomer size. Blocking the chitin‐TLR2 interaction effectively prevents chitin‐mediated inflammation.
Oligomeric chains of fungal chitin directly bind to TLR2 and trigger inflammation.
Blocking of the chitin‐TLR2 interaction prevents chitin‐mediated inflammation in vitro and in vivo.
Size‐dependent chitin recognition based on oligomers is found in both plants and humans.
EMBO Reports (2018) 19: e46065
- Received March 6, 2018.
- Revision received August 31, 2018.
- Accepted September 10, 2018.
- © 2018 The Authors
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