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Isocitrate lyase mediates broad antibiotic tolerance in Mycobacterium tuberculosis
Mycobacterium tuberculosisis intrinsically resistant to most antibiotics. Here, the authors show that the pathogen’s tolerance to three antibiotics, each one targeting a distinct cellular process, is mediated by an antioxidant response that requires the activation of isocitrate lyases.
- Madhumitha Nandakumar
- , Carl Nathan
- & Kyu Y. Rhee
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| Open AccessMolecular basis for bacterial peptidoglycan recognition by LysM domains
Proteins containing LysM domains recognize polysaccharides such as chitin and peptidoglycan, the main components of fungal and bacterial cell walls. Here the authors describe the molecular interactions between peptidoglycan and a LysM domain from the opportunistic bacterial pathogen Enterococcus faecalis.
- Stéphane Mesnage
- , Mariano Dellarole
- & Michael P. Williamson
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| Open AccessPlant genomes enclose footprints of past infections by giant virus relatives
Nucleocytoplasmic large DNA viruses, NCLDVs, are eukaryotic viruses with large genomes, known to infect animals and diverse unicellular eukaryotes. Here, Maumus et al. find NCLDV-like sequences in two land plants and show that they are transcriptionally inactive and highly methylated.
- Florian Maumus
- , Aline Epert
- & Guillaume Blanc
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A mortise–tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes
Bacterial autotransporters are folded in a process that entraps segments of their N-terminal passenger domain. Here, Leyton et al. identify glycine-aromatic mortise and tenon motifs that mediate the passenger domain’s translocation to the bacterial cell surface, and show that the motifs are evolutionarily conserved.
- Denisse L. Leyton
- , Matthew D. Johnson
- & Trevor Lithgow
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Injectable bioadhesive hydrogels with innate antibacterial properties
Bioadhesives are materials frequently used as surgical sealants, though to date, these typically possess limited antibacterial properties. Here, the authors present a novel injectable and antibacterial bioadhesive hydrogel and demonstrate its performance in vivo.
- Michael C. Giano
- , Zuhaib Ibrahim
- & Joel P. Schneider
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| Open AccessFtsZ-independent septal recruitment and function of cell wall remodelling enzymes in chlamydial pathogens
Chlamydiae lack a conventional peptidoglycan cell wall, and yet cell wall remodelling enzymes are largely conserved in these organisms. Frandi et al.identify a chlamydial peptidoglycan endopeptidase, NlpD, and show that it targets the septum of dividing Chlamydiae in a manner dependent on cell wall synthesis.
- Antonio Frandi
- , Nicolas Jacquier
- & Patrick H. Viollier
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| Open AccessAmiA is a penicillin target enzyme with dual activity in the intracellular pathogen Chlamydia pneumoniae
Penicillin inhibits growth of chlamydial pathogens despite their lack of a conventional peptidoglycan cell wall. Here the authors report that the chlamydial amidase, AmiA, which can rescue cell division defects of an E. coli amiAmutant, has dual activity as a penicillin sensitive, lipid II-targetting carboxypeptidase.
- Anna Klöckner
- , Christian Otten
- & Beate Henrichfreise
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Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells
Ganglioside GM3, a cellular lipid included in the envelope of HIV-1 viral particles, interacts with cellular receptor CD169. Here, the authors develop artificial nanoparticles, consisting of a golden core and a GM3-containing synthetic membrane, that recapitulate the CD169-dependent uptake of viral particles.
- Xinwei Yu
- , Amin Feizpour
- & Björn M. Reinhard
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| Open AccessNitrogen stress response and stringent response are coupled in Escherichia coli
The nitrogen regulation stress response and the stringent response are two major regulatory pathways in bacteria, but their mutual coordination is unclear. Here, the authors show that NtrC, the main regulatory protein from the first pathway, activates expression of relA, a key gene from the second pathway.
- Daniel R. Brown
- , Geraint Barton
- & Sivaramesh Wigneshweraraj
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| Open AccessCell cycle transition from S-phase to G1 in Caulobacter is mediated by ancestral virulence regulators
The bacterium Caulobacter crescentus divides asymmetrically to generate a replicative stalk cell and a quiescent swarmer cell. Fumeaux et al. show that MucR zinc-finger transcription factors, which regulate virulence in other species, also control re-entry into quiescence in Caulobacter.
- Coralie Fumeaux
- , Sunish Kumar Radhakrishnan
- & Patrick H. Viollier
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| Open AccessPredicting the risk of avian influenza A H7N9 infection in live-poultry markets across Asia
An avian influenza virus of the H7N9 type, associated with live-poultry markets, has caused two human epidemics in China. Here, the authors develop a statistical model that predicts the risk of H7N9 infection in live-poultry markets across Asia, as a tool for disease surveillance and control.
- Marius Gilbert
- , Nick Golding
- & Hongjie Yu
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Evidence for an electrostatic mechanism of force generation by the bacteriophage T4 DNA packaging motor
Viral DNA packaging motors must generate large forces to package the viral capsid. Here, Migliori et al.provide functional and computational evidence that electrostatic interactions between subdomains of the T4 packaging motor provide the driving force for DNA packaging.
- Amy D. Migliori
- , Nicholas Keller
- & Douglas E. Smith
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Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes albopictus mosquitoes
The ability of a pathogen to adapt to new hosts affects its ability to spread in new environments. Here, Tsetsarkin et al.analysed mutations that enabled the chikungunya virus to adapt to a mosquito vector and predict that specific mutations will result in greater transmission efficiency.
- Konstantin A. Tsetsarkin
- , Rubing Chen
- & Scott C. Weaver
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Stiff filamentous virus translocations through solid-state nanopores
Nanopores are promising tools for the detection and characterization of biomolecules. Here, the authors combine experiments and simulations to study how the passage of rigid viruses through solid-state nanopores differs from more flexible biomolecules.
- Angus McMullen
- , Hendrick W. de Haan
- & Derek Stein
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| Open AccessA barcode of organellar genome polymorphisms identifies the geographic origin of Plasmodium falciparum strains
Tracing the source of malarial infections is an important step towards monitoring and controlling the disease. Here, Preston et al. analyse sequence data from 711 isolates and design a genetic barcode based on combined mitochondrial and apicoplast genomes that is able to distinguish between malaria parasites isolated from different geographical regions.
- Mark D. Preston
- , Susana Campino
- & Taane G. Clark
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Membrane deformation and scission by the HSV-1 nuclear egress complex
Two viral proteins form the nuclear egress complex of herpesviruses, which is essential for the exit of nascent viral capsids from the cell nucleus. Here, the authors use synthetic lipid vesicles to show that the complex can mediate membrane budding in the absence of other cellular factors.
- Janna M. Bigalke
- , Thomas Heuser
- & Ekaterina E. Heldwein
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Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population
Synonymous mutations, nucleotide changes that do not alter the encoded amino acid, are usually seen not to have an effect on organism survival. Here, Bailey et al. show that two synonymous mutations in Pseudomonas fluorescenshad a beneficial effect and acted via increased gene expression.
- Susan F. Bailey
- , Aaron Hinz
- & Rees Kassen
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| Open AccessEvidence of natural Wolbachia infections in field populations of Anopheles gambiae
Wolbachia bacteria live within the cells of many insect species, manipulating their hosts’ reproduction and immune responses. Here, the authors show that these microbes also infect wild populations of malaria-spreading Anopheles mosquitoes, supporting a potential use of Wolbachiato limit malaria transmission.
- Francesco Baldini
- , Nicola Segata
- & Flaminia Catteruccia
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Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences
Phosphorothioate (PT) DNA modifications are widespread in bacteria and play a critical role in cell physiology. Here, the authors develop two sequence-based technologies to map PT modifications across bacterial genomes.
- Bo Cao
- , Chao Chen
- & Peter C. Dedon
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Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action
Atovaquone is an antimalarial drug that inhibits a crucial enzyme, cytochrome bc1complex, within the parasite’s mitochondria. Here the authors report the crystal structure of the enzyme with bound atovaquone, opening the way for rational development of improved antimalarial drugs.
- Dominic Birth
- , Wei-Chun Kao
- & Carola Hunte
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Centrin3 in trypanosomes maintains the stability of a flagellar inner-arm dynein for cell motility
Beating flagella are essential for the locomotion of Trypanosoma brucei, the causative agent of human sleeping sickness. Here, Wei et al. identify a role for one of five centrin proteins, TbCentrin3, in stabilizing the assembly of a dynein motor essential for flagellar motility.
- Ying Wei
- , Huiqing Hu
- & Ziyin Li
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| Open AccessIntegrating artificial with natural cells to translate chemical messages that direct E. coli behaviour
The control of cellular behaviour largely relies on genetic engineering, but artificial cells could be designed to control cell processes through chemical communication. Here, the authors develop an artificial cell that is able to translate a chemical message into a signal that can be sensed by E. coliand activate a cellular response.
- Roberta Lentini
- , Silvia Perez Santero
- & Sheref S. Mansy
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Persistent super-diffusive motion of Escherichia coli chromosomal loci
In bacteria, chromosomal architecture exhibits spatial and temporal fluctuations, which affect cellular functions. Here, Javer et al. use high-resolution tracking of chromosomal loci in E. colito uncover rare events of unusually large and fast movements, providing new insight into bacterial chromosome dynamics.
- Avelino Javer
- , Nathan J. Kuwada
- & Marco Cosentino Lagomarsino
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| Open AccessA global non-coding RNA system modulates fission yeast protein levels in response to stress
Non-coding RNAs are widely expressed, yet their functions remain poorly understood. Here, Leong et al. identify a set of antisense RNAs elevated during the yeast stress response that directly correlate with reduced protein levels, indicating a general regulatory effect of antisense expression.
- Hui Sun Leong
- , Keren Dawson
- & Crispin J. Miller
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| Open AccessMobile elements drive recombination hotspots in the core genome of Staphylococcus aureus
Horizontal gene transfer occurs in most bacteria, yet it is unclear whether it happens in clonal species. Here, Everitt et al. show widespread within-species recombination, driven by mobile elements, in the genome of the pathogen Staphylococcus aureus, but no recombination between closely related strains.
- Richard G. Everitt
- , Xavier Didelot
- & Daniel J. Wilson
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High specificity in plant leaf metabolic responses to arbuscular mycorrhiza
Plant species share a core metabolome, however the extent to which metabolic responses to environmental cues are also conserved remains unclear. Schweiger et al.describe shifts in the leaf metabolomes of five plant species during mycorrhizal fungal infection, and uncover high species-specificity.
- Rabea Schweiger
- , Markus C. Baier
- & Caroline Müller
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| Open AccessPhysiological and genomic features of highly alkaliphilic hydrogen-utilizing Betaproteobacteria from a continental serpentinizing site
Microbes can dwell in highly alkaline environments in the absence of obvious food sources. Here, the authors describe physiological and genomic features of a group of bacteria that live on hydrogen, calcium carbonate and oxygen at a very high pH.
- Shino Suzuki
- , J. Gijs Kuenen
- & Kenneth H. Nealson
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Evidence of global-scale aeolian dispersal and endemism in isolated geothermal microbial communities of Antarctica
Geographical isolation is often considered an effective barrier to microbial transport. Here, the authors provide evidence of active recruitment of long-distance dispersed cosmopolitan microorganisms in fumarolic environments in Mount Erebus, Antarctica.
- Craig W. Herbold
- , Charles K. Lee
- & S. Craig Cary
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A toggle switch controls the low pH-triggered rearrangement and maturation of the dengue virus envelope proteins
Formation of infectious dengue virus in host cells requires a rearrangement of viral envelope proteins that is triggered by the acidic environment within secretory vesicles. Here, the authors describe the molecular mechanism underlying such rearrangement.
- Aihua Zheng
- , Fei Yuan
- & Margaret Kielian
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The curved shape of Caulobacter crescentus enhances surface colonization in flow
The potential advantages of specific cell shapes among microbes are unclear. Here, the authors show that the curved shape of the bacterium Caulobacter crescentus, which lives in lakes and streams, helps cells to colonize surfaces in the presence of fluid flow.
- Alexandre Persat
- , Howard A. Stone
- & Zemer Gitai
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Structural basis of PcsB-mediated cell separation in Streptococcus pneumoniae
The peptidoglycan hydrolase PcsB is required for cell wall splitting during cell division in Streptococci. Bartual et al.show that PcsB adopts an autoinhibited dimeric structure, and demonstrate the muralytic activity of the uninhibited catalytic domain.
- Sergio G. Bartual
- , Daniel Straume
- & Juan A. Hermoso
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Bacterial twitching motility is coordinated by a two-dimensional tug-of-war with directional memory
Bacteria such as Neisseria gonorrhoeaeuse filamentous appendages known as pili to move on surfaces. Here, using a combined theoretical and experimental approach, the authors show that pili are coordinated through a tug-of-war mechanism that provides directional persistence.
- Rahul Marathe
- , Claudia Meel
- & Stefan Klumpp
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Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections
H5N1 avian influenza viruses can be highly pathogenic. Here, the authors show that H5N1 infection leads to increased serum levels of angiotensin II in patients and mice, and that administration of angiotensin-converting enzyme 2 ameliorates lung injury in infected mice.
- Zhen Zou
- , Yiwu Yan
- & Chengyu Jiang
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| Open AccessThe malaria parasite egress protease SUB1 is a calcium-dependent redox switch subtilisin
In the malarial parasitophorous vacuole, the serine protease SUB1 processes parasite proteins that are required for release from host cells and invasion. Here, the authors report the first crystallographic structure of SUB1 in complex with its cognate prodomain revealing its substrate interactions and providing insight into its regulation.
- Chrislaine Withers-Martinez
- , Malcolm Strath
- & Michael J. Blackman
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| Open AccessMutation rate plasticity in rifampicin resistance depends on Escherichia coli cell–cell interactions
The factors varying mutation rate at a particular site in a single genotype remain elusive. Here, Krašovec et al. show that mutation rates at sites conferring resistance to rifampicin in Escherichia coli decrease with population density, and that mutation-rate plasticity is controlled by the luxSgene.
- Rok Krašovec
- , Roman V. Belavkin
- & Christopher G. Knight
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Crystal structure of listeriolysin O reveals molecular details of oligomerization and pore formation
The cytolysin, listeriolysin O (LLO), is expressed by Listeria and forms pores in the phagosomal membrane in response to decreased pH. Here, Yildiz et al. solve the crystal structure of LLO, identify residues that serve as the pH sensor, and determine the mechanism of pore formation in host membranes.
- Stefan Köster
- , Katharina van Pee
- & Özkan Yildiz
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| Open AccessAdjustment of microbial nitrogen use efficiency to carbon:nitrogen imbalances regulates soil nitrogen cycling
Nitrogen availability in soils is predominantly controlled by microorganisms, yet our understanding of their organic nitrogen use is limited. Mooshammer et al.show that microbial nitrogen use efficiency is dependent on resource stoichiometry and substrate type.
- Maria Mooshammer
- , Wolfgang Wanek
- & Andreas Richter
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MicroRNA-302b augments host defense to bacteria by regulating inflammatory responses via feedback to TLR/IRAK4 circuits
Bacterial infection stimulates a powerful inflammatory response that must be regulated to prevent tissue damage. Zhou et al.identify microRNA-302b as a feedback suppressor of inflammatory signalling that alleviates lung injury following Pseudomonas infection by targeting the NF-κB activator IRAK4.
- Xikun Zhou
- , Xuefeng Li
- & Min Wu
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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
| Open AccessCell wall precursors are required to organize the chlamydial division septum
Cell division in Chlamydiales remains mysterious as it occurs in the absence of a cytokinetic tubulin and a classical peptidoglycan cell wall. Jacquier et al. show that the actin homologue MreB is recruited to the division site in Waddliaand that this depends on synthesis of the peptidoglycan precursor lipid II.
- Nicolas Jacquier
- , Antonio Frandi
- & Gilbert Greub
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Lactate racemase is a nickel-dependent enzyme activated by a widespread maturation system
Lactate racemase is an enzyme that interconverts the L and D isomers of the common metabolite lactate. Here, the authors show that lactate racemase represents a new type of nickel-dependent enzyme, which is activated by accessory proteins that are widespread among prokaryotic microbes.
- Benoît Desguin
- , Philippe Goffin
- & Pascal Hols
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Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen
Semen-derived peptides can form amyloid fibrils that boost HIV infection in vitro, but the existence of such fibrils in semen remained to be demonstrated. Here, the authors show that human semen contains amyloid fibrils, which can bind HIV particles and increase their infectiveness.
- Shariq M. Usmani
- , Onofrio Zirafi
- & Jan Münch
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| Open AccessThe Vibrio cholerae type VI secretion system employs diverse effector modules for intraspecific competition
Some strains of the pathogen Vibrio choleraecan kill each other by injecting effector proteins that are toxic in the absence of cognate ‘immunity’ proteins. Here, the authors show that strains with high pathogenic potential possess matching effector-immunity sets and can coexist.
- Daniel Unterweger
- , Sarah T. Miyata
- & Stefan Pukatzki
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Molecular basis for erythromycin-dependent ribosome stalling during translation of the ErmBL leader peptide
In bacteria, the ribosomal stalling during translation of leader peptides is a mechanism of antibiotic resistance that has not been well understood. Here, the structure of a drug-dependent stalled ribosome complex has allowed the authors to propose a detailed mechanism for this translational arrest.
- Stefan Arenz
- , Haripriya Ramu
- & Daniel N. Wilson
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Article
| Open AccessThe actin homologue MreB organizes the bacterial cell membrane
The formation of lipid domains in eukaryotic cells is controlled by the cortical actin cytoskeleton. Here, the authors show that the bacterial actin homologue MreB has a comparable activity, influencing the formation of regions of increased fluidity that determine the distribution of membrane proteins.
- Henrik Strahl
- , Frank Bürmann
- & Leendert W. Hamoen
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| Open AccessCBR antimicrobials alter coupling between the bridge helix and the β subunit in RNA polymerase
Bacterial RNA polymerase (RNAP) is crucial for cellular gene expression and a validated target for antimicrobial drugs. Here, Malinen et al. explore the effects of the CBR class of RNAP inhibitors on the E. coliRNAP transcription cycle and provide detailed mechanistic insight into their antibacterial action.
- Anssi M. Malinen
- , Monali NandyMazumdar
- & Georgiy A Belogurov
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| Open AccessDelayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism
The delayed onset of bactericidal activity of the anti-tuberculosis antibiotic bedaquiline is puzzling. Here, Koul and colleagues show, using a multi-omics approach, that the drug triggers a metabolic remodelling in Mycobacterium tuberculosisthat enables the pathogen’s transient survival.
- Anil Koul
- , Luc Vranckx
- & Dirk Bald
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Electron uptake by iron-oxidizing phototrophic bacteria
Little is known about extracellular electron uptake by microbes. Here Bose et al. show that the anoxygenic photoautotroph Rhodopseudomonas palustrisTIE-1 accepts electrons from a poised electrode, which can be uncoupled from photosynthesis, and the pioABC system has a role in this uptake.
- A. Bose
- , E.J. Gardel
- & P.R. Girguis
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Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon
Enterovirus 71 (EV71) is one of the causative agents of hand-food-mouth disease and to date, effective vaccines or antivirals against the disease have not been developed. Here, the authors show that blocking miR-146a upregulation induced upon EV71 infection can have a positive effect on the resolution of infection.
- Bing-Ching Ho
- , I-Shing Yu
- & Sung-Liang Yu
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