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| Open AccessToxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome
MazF endoribonucleases are thought to arrest growth of Mycobacterium tuberculosis by global translation inhibition. Here, Barth et al. show that MazF-mt9 cleaves a specific tRNA, leading to ribosome stalling at AAA codons and thus selective mRNA degradation and changes in transcriptome and proteome.
- Valdir C. Barth
- , Ju-Mei Zeng
- & Nancy A. Woychik
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Article
| Open AccessThe pore structure of Clostridium perfringens epsilon toxin
Epsilon toxin (Etx) is a potent pore forming toxin (PFT) produced by Clostridium perfringens. Here authors show the cryo-EM structure of the Etx pore assembled on the membrane of susceptible cells and shed light on pore formation and mutant phenotypes.
- Christos G. Savva
- , Alice R. Clark
- & Monika Bokori-Brown
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Article
| Open AccessEnvironmental pH and peptide signaling control virulence of Streptococcus pyogenes via a quorum-sensing pathway
The mechanism by which environmental pH controls the virulence of the pathogen Streptococcus pyogenes is unclear. Here, Do et al. show that changes in pH affect the activity of the virulence regulator RopB via its interaction with a quorum-sensing peptide signal.
- Hackwon Do
- , Nishanth Makthal
- & Muthiah Kumaraswami
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Article
| Open AccessCryo-EM structures of the pore-forming A subunit from the Yersinia entomophaga ABC toxin
YenTcA is the pore-forming and membrane binding subunit of the ABC toxin YenTc, which is produced by the insect pathogen Yersinia entomophaga. Here authors present cryo-EM structures of YenTcA purified from the native source which implicate associated endochitinases in host cell recognition.
- Sarah J Piper
- , Lou Brillault
- & Michael J Landsberg
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Article
| Open Access14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface
The cellular toxicity of Pseudomonas exotoxin-S and -T depends on their activation by 14-3-3 but the underlying molecular mechanism is not fully understood. Here, the authors show that a previously unrecognized 14-3-3:exotoxin binding interface is sufficient for complex formation and toxin activation.
- Tobias Karlberg
- , Peter Hornyak
- & Herwig Schüler
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Article
| Open AccessStructures of Teneurin adhesion receptors reveal an ancient fold for cell-cell interaction
Teneurins are cell-cell adhesion receptors that evolved through horizontal gene transfer in which a bacterial YD-repeat protein fused to a eukaryotic receptor. Here the authors present crystallographic and cryo-EM structures of two Teneurins, revealing an ancient YD-repeat protein super-fold.
- Verity A. Jackson
- , Dimphna H. Meijer
- & Elena Seiradake
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Article
| Open AccessThe protease GtgE from Salmonella exclusively targets inactive Rab GTPases
The bacterial protease GtgE is involved in the establishment of Salmonellosis. Here the authors provide a structural and biochemical analysis of GtgE that sheds light on the molecular mechanisms of reprogramming infected host cells via site-specific proteolytic cleavage of the vesicular trafficking regulator Rab32.
- Rudolf Wachtel
- , Bastian Bräuning
- & Aymelt Itzen
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Article
| Open AccessStaphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314
Bacterial infection can cause pain but the underlying mechanism is unclear. This study shows pain induced in mice by methicillin-resistant Staphylococcus aureus infection is mediated by bacterial pore-forming toxins, and a sodium channel blocker QX-314 can alleviate infection-associated pain.
- Kimbria J. Blake
- , Pankaj Baral
- & Isaac M. Chiu
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Article
| Open AccessInterspecies nutrient extraction and toxin delivery between bacteria
Bacteria can exchange nutrients and macromolecules through tubular membranous structures called nanotubes. Here, the authors show that Bacillus subtilis can kill and prey on Bacillus megaterium by delivering a toxin and extracting nutrients in a nanotube-dependent manner.
- Ofer Stempler
- , Amit K. Baidya
- & Sigal Ben-Yehuda
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Article
| Open AccessActin activates Pseudomonas aeruginosa ExoY nucleotidyl cyclase toxin and ExoY-like effector domains from MARTX toxins
The ExoY toxin is injected by Pseudomonas aeruginosainto host cells, where it is activated by an unknown host factor. Here the authors identify such factor as filamentous actin.
- Alexander Belyy
- , Dorothée Raoux-Barbot
- & Undine Mechold
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Article
| Open AccessCryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process
Aerolysin is a secreted bacterial pore forming toxin that inserts into the host plasma membrane, potentially leading to cell death. Here the authors present Cryo-EM structures of aerolysin arrested at different stages of the pore formation process that provide insight into the conformational changes that allow pore formation.
- Ioan Iacovache
- , Sacha De Carlo
- & Benoît Zuber
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Article
| Open AccessAutophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity
The MARTX toxin of V. choleraeprocesses itself to deliver three distinct effector domains to the cytosol. Here the authors show that the third effector domain is a phosphatidylinositol-3-phosphate (PtdIns3P)-specific phospholipase that inhibits autophagy in target cells.
- Shivani Agarwal
- , Hyunjin Kim
- & Karla J. F. Satchell
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Article
| Open AccessCounter inhibition between leukotoxins attenuates Staphylococcus aureus virulence
Staphylococcus aureusstrains produce a family of highly related toxins that puncture the cytoplasmic membrane of susceptible cells. Here, Yoong and Torres show that the toxins can counteract each other in a cell type-dependent manner by forming inactive hybrid complexes, thus modulatingS. aureusvirulence.
- Pauline Yoong
- & Victor J. Torres
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Article
| Open AccessGenetic, molecular and physiological basis of variation in Drosophila gut immunocompetence
Animals rely on a multitude of resistance and tolerance mechanisms to resist harmful gut microbes. Here, the authors explore the genetic, molecular and physiological basis underlying the remarkable phenotypic variation in resistance to enteric bacterial infection inDrosophila melanogaster.
- Maroun S. Bou Sleiman
- , Dani Osman
- & Bart Deplancke
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Article |
Growth-regulating Mycobacterium tuberculosis VapC-mt4 toxin is an isoacceptor-specific tRNase
Toxin–antitoxin systems of the Vap class regulate the growth of several bacterial pathogens including Mycobacterium tuberculosis. Here, the authors show that toxin VapC-mt4 arrests M. tuberculosis growth by specifically cleaving three tRNAs at a single site in their anticodon stem loop, leading to translation inhibition.
- Jonathan W. Cruz
- , Jared D. Sharp
- & Nancy A. Woychik
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Article
| Open AccessContext influences on TALE–DNA binding revealed by quantitative profiling
TALE proteins are popular tools for genome engineering because they can recognize specific DNA sequences, however off-target effects are a routine problem. Here Rogers and Barrera et al. comprehensively map TALE–DNA interactions to develop a computational model to predict binding specificity.
- Julia M. Rogers
- , Luis A. Barrera
- & Martha L. Bulyk
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Article
| Open AccessThe assembly dynamics of the cytolytic pore toxin ClyA
Pore-forming toxins are expressed as monomers and assemble into multimeric pores. Here, Benke et al. follow the kinetics of pore formation for the bacterial toxin ClyA with single-molecule methods and show that pore formation progresses through the assembly of oligomeric intermediates, rather than by the addition of monomers to a nascent pore.
- Stephan Benke
- , Daniel Roderer
- & Benjamin Schuler
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The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors
Genes encoding two pore-forming toxins (γ-haemolysins HlgAB and HlgCB) are present in almost all human Staphylococcus aureus isolates. Here Spaan et al.show that HlgAB and HlgCB target different phagocyte types by interacting with specific chemokine receptors and complement receptors, respectively.
- András N. Spaan
- , Manouk Vrieling
- & Thomas Henry
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An RNA-seq method for defining endoribonuclease cleavage specificity identifies dual rRNA substrates for toxin MazF-mt3
MazF toxins inhibit bacterial growth by cleaving single-stranded RNA at specific sequences. Here, the authors describe a new genome-wide approach, MORE RNA-seq, for defining MazF cleavage specificity, and show that MazF-mt3 cleaves 23S and 16S ribosomal RNAs.
- Jason M. Schifano
- , Irina O. Vvedenskaya
- & Nancy A Woychik
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Article |
Autotransporters but not pAA are critical for rabbit colonization by Shiga toxin-producing Escherichia coli O104:H4
An outbreak of diarrhoea and haemolytic uraemic syndrome in Germany in 2011 was caused by a Shiga toxin-producing enteroaggregative E. coli, which carried the aggregative adherence plasmid pAA. Here, the authors show that autotransporters, but not pAA, are required for intestinal colonization in an infant rabbit model.
- Diana Munera
- , Jennifer M. Ritchie
- & Matthew K. Waldor
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Cytotoxicity of botulinum neurotoxins reveals a direct role of syntaxin 1 and SNAP-25 in neuron survival
Botulinum toxins can cause substantial neurodegeneration. Peng et al. study cultured rat hippocampal neurons and find that botulinum toxin-induced cytotoxicity occurs only when there is effective cleavage of the SNARE proteins, syntaxin 1 or SNAP-25, by type C and type E botulinum toxins.
- Lisheng Peng
- , Huisheng Liu
- & Min Dong