Microbiology, Virology & Host Pathogen Interaction
- Vesicular stomatitis virus N protein‐specific single‐domain antibody fragments inhibit replication
- Leo Hanke1,
- Florian I Schmidt1,4,
- Kevin E Knockenhauer2,
- Benjamin Morin3,
- Sean PJ Whelan3,
- Thomas U Schwartz2 and
- Hidde L Ploegh (hidde.ploegh{at}childrens.harvard.edu)*,1,2,5
- 1Whitehead Institute for Biomedical Research, Cambridge, MA, USA
- 2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
- 3Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
- 4Present Address: Institute of Innate Immunity, University of Bonn, Bonn, Germany
- 5Present Address: Boston Children's Hospital, Boston, MA, USA
- ↵*Corresponding author. Tel: +1 617 919 1613; E‐mail: hidde.ploegh{at}childrens.harvard.edu
Nanobodies are promising tools to target and study RNA viruses. In this study the binding sites of alpaca single‐domain antibodies on the vesicular stomatitis virus are determined and their antiviral activity is analyzed using escape mutants.
Synopsis
Nanobodies are promising tools to target and study RNA viruses. In this study the binding sites of alpaca single‐domain antibodies on the vesicular stomatitis virus are determined and their antiviral activity is analyzed using escape mutants.
VHH 1004 binds to the N‐terminal lobe of N, inhibits replication but not primary transcription, and decorates the 10‐mer N‐RNA ring.
VHH 1307 binds to the C‐terminal lobe of N, competes with the C‐terminal domain of P for binding, and prevents primary transcription.
VHH 1001 binds to a different epitope on the C‐terminal lobe of N, competes with a different part of P, and prevents primary transcription.
EMBO Reports (2017) 18: 1027–1037
- Received December 6, 2016.
- Revision received March 8, 2017.
- Accepted March 13, 2017.
- © 2017 The Authors
- RNA activation‐independent DNA targeting of the Type III CRISPR‐Cas system by a Csm complex
- Kwang‐Hyun Park1,
- Yan An1,
- Tae‐Yang Jung2,3,4,
- In‐Young Baek1,
- Haemin Noh2,
- Woo‐Chan Ahn1,2,
- Hans Hebert3,4,
- Ji‐Joon Song2,
- Jeong‐Hoon Kim5,
- Byung‐Ha Oh (bhoh{at}kaist.ac.kr)*,2 and
- Eui‐Jeon Woo (ejwoo{at}kribb.re.kr)*,1,6
- 1Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea
- 2Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST) Institute for the BioCentury, Daejeon, South Korea
- 3Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden
- 4School of Technology and Health, KTH Royal Institute of Technology, Huddinge, Sweden
- 5Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea
- 6Department of Analytical Bioscience, University of Science and Technology, Daejeon, South Korea
- ↵*
Corresponding author. Tel: +82 423502648; E‐mail: bhoh{at}kaist.ac.kr
Corresponding author. Tel: +82 428798432; E‐mail: ejwoo{at}kribb.re.kr
The Type III CRISPR‐Cas system in T. onnurineus cleaves target ssDNA in a direct cis‐acting and target RNA‐independent manner, suggesting a novel ssDNA targeting mechanism of the Type III system.
Synopsis
The Type III CRISPR‐Cas system in T. onnurineus cleaves target ssDNA in a direct cis‐acting and target RNA‐independent manner, suggesting a novel ssDNA targeting mechanism of the Type III system.
The Csm effector complex of T. onnurineus was reconstituted with a minimalistic combination of Csm1121334151.
The complex shows RNA targeting and RNA‐activated ssDNA targeting activities.
The complex shows RNA activation‐independent ssDNA targeting activity that requires the HD domain of the Csm1 subunit.
EMBO Reports (2017) 18: 826–840
- Received November 20, 2016.
- Revision received February 19, 2017.
- Accepted February 23, 2017.
- © 2017 The Authors
- In situ structure of the Legionella Dot/Icm type IV secretion system by electron cryotomography
- Debnath Ghosal1,
- Yi‐Wei Chang1,
- Kwangcheol C Jeong2,4,
- Joseph P Vogel2 and
- Grant J Jensen (jensen{at}caltech.edu)*,1,3
- 1California Institute of Technology, Pasadena, CA, USA
- 2Washington University School of Medicine, St. Louis, MO, USA
- 3Howard Hughes Medical Institute, Pasadena, CA, USA
- 4University of Florida, Gainesville, FL, USA
- ↵*Corresponding author. Tel: +1 626 395 8827; E‐mail: jensen{at}caltech.edu
Bacterial type IV secretion systems translocate protein and DNA, and are involved in the pathogenesis of multiple human diseases. This study presents the in situ structure of the Dot/Icm type IVB secretion system from the human pathogen Legionella pneumophila.
Synopsis
Bacterial type IV secretion systems translocate protein and DNA, and are involved in the pathogenesis of multiple human diseases. This study presents the in situ structure of the Dot/Icm type IVB secretion system from the human pathogen Legionella pneumophila.
First structure of a type IVB secretion system, and also the first structure of any T4SS in situ.
The Dot/Icm system shares almost no sequence similarity with type IVA secretion systems (T4ASSs).
The basic architecture of the type IVB secretion system is however strikingly similar to the type IVA secretion system.
EMBO Reports (2017) 18: 726–732
- Received October 29, 2016.
- Revision received February 15, 2017.
- Accepted February 21, 2017.
- © 2017 The Authors
- Molecular architecture of the N‐type ATPase rotor ring from Burkholderia pseudomallei
- Sarah Schulz1,†,
- Martin Wilkes1,†,
- Deryck J Mills1,
- Werner Kühlbrandt1 and
- Thomas Meier (t.meier{at}imperial.ac.uk)*,1,2
- 1Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
- 2Department of Life Sciences, Imperial College London, London, UK
- ↵*Corresponding author. Tel: +44 2075943056; E‐mail: t.meier{at}imperial.ac.uk
↵† These authors contributed equally to this work
This study describes the molecular architecture of the N‐type ATPase rotor ring from Burkholderia pseudomallei determined by electron cryo‐microscopy. The structure shows an unusually large c‐ring rotor with 17 subunits that is driven predominantly by protons.
Synopsis
This study describes the molecular architecture of the N‐type ATPase rotor ring from Burkholderia pseudomallei determined by electron cryo‐microscopy. The structure shows an unusually large c‐ring rotor with 17 subunits that is driven predominantly by protons.
Burkholderia pseudomallei expresses a N‐type rotary ATPase, in addition to the regular F‐type rotary ATPase.
The N‐type ATPase rotor ring consists of 17 identical copies of c‐subunits and preferentially binds protons.
The N‐type ATPase is optimized for bacterial survival in the host phagosome and may be instrumental for infection.
EMBO Reports (2017) 18: 526–535
- Received September 19, 2016.
- Revision received February 2, 2017.
- Accepted February 9, 2017.
- © 2017 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.
- Regulating phage therapyThe biological master file concept could help to overcome regulatory challenge of personalized medicines
The biological master file concept could help to overcome regulatory challenge of personalized medicines
- Alan Fauconnier (alan.fauconnier{at}invivo.be)1
The clinical use of bacteriophages to treat bacterial infections faces regulatory difficulties in the EU. The ‘Biological Master File’ concept could overcome these hurdles for phage therapy as well as other personalized medicines.
- © 2017 The Author
- Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore‐forming toxins
- Francisco Sarmento Mesquita1,2,
- Cláudia Brito1,2,3,
- Maria J Mazon Moya4,
- Jorge Campos Pinheiro1,2,3,
- Serge Mostowy4,
- Didier Cabanes (didier{at}ibmc.up.pt)*,1,2 and
- Sandra Sousa (srsousa{at}ibmc.up.pt)*,1,2
- 1I3S‐Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- 2Group of Molecular Microbiology, IBMC, Universidade do Porto, Porto, Portugal
- 3Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal
- 4Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection (CMBI), Imperial College London, London, UK
- ↵*
Corresponding author. Tel: +351 220 408 800; E‐mail: didier{at}ibmc.up.pt
Corresponding author. Tel: +351 220 408 800; E‐mail: srsousa{at}ibmc.up.pt
Gp96 plays a role in actomyosin remodelling and coordination of plasma membrane blebbing triggered by pore‐forming toxins. This process protects membrane integrity and host survival during infection and has implications in cytoskeletal organization.
Synopsis
Gp96 plays a role in actomyosin remodelling and coordination of plasma membrane blebbing triggered by pore‐forming toxins. This process protects membrane integrity and host survival during infection and has implications in cytoskeletal organization.
Gp96 controls NMHCIIA network and NMII activity during PFT‐induced PM blebbing.
Gp96 and NMHCIIA protect PM integrity against bacterial PFT‐mediated damage.
Gp96–NMHCIIA interplay during PFT responses resembles polarized cell migration process.
Gp96 promotes host survival during in vivo Listeria infection.
EMBO Reports (2017) 18: 303–318
- Received June 3, 2016.
- Revision received November 16, 2016.
- Accepted November 18, 2016.
- © 2016 The Authors
- Domestication of a housekeeping transglycosylase for assembly of a Type VI secretion system
- 1Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM), UMR 7255, Institut de Microbiologie de la Méditerranée, Aix‐Marseille Univ – CNRS, Marseille Cedex 20, France
- ↵*Corresponding author. Tel: +33 491164504; E‐mail: cascales{at}imm.cnrs.fr
The bacterial type VI secretion system (T6SS) comprises a contractile tail anchored to the cell envelope. This study shows that the housekeeping peptidoglycan hydrolase MltE is recruited to the T6SS and stimulated by the TssM subunit to create membrane lesions for the proper assembly of the trans‐envelope complex.
Synopsis
The bacterial Type VI secretion system (T6SS) comprises a contractile tail anchored to the cell envelope. This study shows that the housekeeping peptidoglycan hydrolase MltE is recruited to the T6SS and stimulated by the TssM subunit to create membrane lesions for the proper assembly of the trans‐envelope complex.
Proper function of the type VI secretion apparatus requires cell wall degradation.
The housekeeping transglycosylase MltE is recruited to and activated by the T6SS membrane complex.
A lytic transglycosylase encoded within the core bacterial genome is domesticated for the assembly of a secretion system.
EMBO Reports (2017) 18: 138–149
- Received August 19, 2016.
- Revision received October 27, 2016.
- Accepted October 28, 2016.
- © 2016 The Authors
- Una destinatio, viae diversaeDoes exposure to the vaginal microbiota confer health benefits to the infant, and does lack of exposure confer disease risk?
Does exposure to the vaginal microbiota confer health benefits to the infant, and does lack of exposure confer disease risk?
- 1Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA
- 2Center for Metagenomics & Microbiome Research, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA
- 3Department of Molecular & Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA
- 4Department of Molecular & Cell Biology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA
↵† These authors contributed equally to this work
There are lingering concerns that Cesarean surgery could impede on the child's health due to a lack of exposure to the mother's vaginal microbiota. However, the evidence so far is not sufficient to affirm whether the mode of birth influences disease risk or whether it is other causes.
- © 2016 The Authors
- Peroxisomal protein PEX13 functions in selective autophagy
- Ming Y Lee1,
- Rhea Sumpter Jr1,
- Zhongju Zou1,2,
- Shyam Sirasanagandla1,
- Yongjie Wei1,2,
- Prashant Mishra3,
- Hendrik Rosewich4,
- Denis I Crane5 and
- Beth Levine (beth.levine{at}utsouthwestern.edu)*,1,2,6
- 1Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
- 2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA
- 3Children's Medical Center Research Institute at the University of Texas Southwestern Medical Center, Dallas, TX, USA
- 4Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany
- 5Eskitis Institute for Drug Discovery and School of Natural Sciences Griffith University, Nathan, Qld, Australia
- 6Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- ↵*Corresponding author. Tel: +1 214 648 2202; E‐mail: beth.levine{at}utsouthwestern.edu
PEX13 is a peroxisomal membrane protein that regulates matrix protein import during peroxisome biogenesis. This study shows that PEX13 and also PEX3 specifically regulate selective autophagy. Mutations in PEX13 lead to dysregulation of autophagy and might therefore contribute to the pathogenesis of Zellweger syndrome spectrum disorders.
Synopsis
PEX13 is a peroxisomal membrane protein that regulates matrix protein import during peroxisome biogenesis. This study shows that PEX13 and also PEX3 specifically regulate selective autophagy. Mutations in PEX13 lead to dysregulation of autophagy and might therefore contribute to the pathogenesis of Zellweger syndrome spectrum disorders.
PEX13 is required for selective virophagy and mitophagy, but not general autophagy.
The selective mitophagy function of PEX13 is shared with PEX3, another peroxin family member, but not with PEX14 and PEX19.
PEX13 mutants I326T and W313G associated with Zellweger syndrome spectrum disorders are defective in mitophagy.
EMBO Reports (2017) 18: 48–60
- Received March 26, 2016.
- Revision received October 4, 2016.
- Accepted October 7, 2016.
- © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- Plant microbiomes and sustainable agricultureDeciphering the plant microbiome and its role in nutrient supply and plant immunity has great potential to reduce the use of fertilizers and biocides in agriculture
Deciphering the plant microbiome and its role in nutrient supply and plant immunity has great potential to reduce the use of fertilizers and biocides in agriculture
- Philip Hunter, Freelance journalist (ph{at}philiphunter.com)1
Plant microbiota play a crucial role by helping their host plant extract nutrients and defend against pathogens. Understanding these mutually beneficial relationships can greatly improve sustainable agriculture.
- © 2016 The Author
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