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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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African origin of the malaria parasite Plasmodium vivax
Plasmodium vivax, the leading cause of human malaria in Asia and Latin America, is thought to have an Asian origin. Here, the authors show that wild chimpanzees and gorillas in Africa are infected with parasites that are closely related to P. vivax, indicating an African origin for this species.
- Weimin Liu
- , Yingying Li
- & Paul M. Sharp
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| Open AccessPopulation genomics supports baculoviruses as vectors of horizontal transfer of insect transposons
Horizontal transfer of DNA is common among eukaryotes but the vectors involved remain elusive. Here, Gilbert et al. show high frequency of in vivotransposition from the cabbage looper moth into genomes of a baculovirus, suggesting that viruses can act as vectors of horizontal transfer between animals.
- Clément Gilbert
- , Aurélien Chateigner
- & Richard Cordaux
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An asymmetric heterodomain interface stabilizes a response regulator–DNA complex
Bacterial two-component systems relay extracellular signals to transcriptional networks via response regulators. Narayanan et al.present structures of the response regulator KdpE bound to DNA, and show that asymmetric interactions between the receiver and DNA-binding domains are required to sustain gene expression.
- Anoop Narayanan
- , Shivesh Kumar
- & Dinesh A. Yernool
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Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus
To successfully replicate and propagate, viruses hijack different components of the host cell machinery. Here, Zhou et al.identify the RNA-binding protein Fragile X mental retardation protein as a host factor involved in influenza A virus replication in host cells.
- Zhuo Zhou
- , Mengmeng Cao
- & Tao Deng
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Integrated circuit-based electrochemical sensor for spatially resolved detection of redox-active metabolites in biofilms
The direct detection of metabolites secreted by cells can indicate how cellular dynamics affects population development. Here, the authors present an integrated circuit-based method for electrochemical imaging of redox-active signalling molecules with spatial resolution within bacterial colonies.
- Daniel L. Bellin
- , Hassan Sakhtah
- & Kenneth L. Shepard
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Microbial iron uptake as a mechanism for dispersing iron from deep-sea hydrothermal vents
Iron emitted from hydrothermal vents is stabilized by organic matter and dispersed into the world ocean, yet the pathways leading to iron–carbon interactions are unknown. Dick et al.propose that a new ‘microbial iron pump’ is responsible for converting hydrothermal iron into bioavailable forms.
- Meng Li
- , Brandy M. Toner
- & Gregory J. Dick
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Photoautotrophic hydrogen production by eukaryotic microalgae under aerobic conditions
Eukaryotic algae and cyanobacteria can produce hydrogen in the presence of little or no oxygen. Here, the authors show that two microalgal strains are capable of producing hydrogen under aerobic conditions, and provide new insights into the natural evolution of oxygen-tolerant hydrogenase.
- Jae-Hoon Hwang
- , Hyun-Chul Kim
- & Byong-Hun Jeon
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Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol
Organisms can adapt to environmental change but how this affects metabolism is unclear. Here, the authors provide a detailed analysis of the effects of individual adaptive mutations on the metabolic network in E. coli, and find evidence of metabolic reprogramming during laboratory evolution on glycerol.
- Kian-Kai Cheng
- , Baek-Seok Lee
- & Martin Robert
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| Open Access4′-O-substitutions determine selectivity of aminoglycoside antibiotics
Aminoglycoside antibiotics target the ribosome but their limited selectivity for the bacterial ribosome can cause side effects in humans. Here, the authors synthesize 4′-O-ether or 4′,6′-O-acetal modifications and show that these compounds possess increased selectivity against bacterial ribosomes.
- Déborah Perez-Fernandez
- , Dmitri Shcherbakov
- & Erik C. Böttger
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Dynamic reassortments and genetic heterogeneity of the human-infecting influenza A (H7N9) virus
H7N9 influenza A viruses capable of infecting humans have recently emerged in China. Here, the authors show that these viruses remain genetically diverse, suggesting that they are still in the process of adapting to human hosts.
- Lunbiao Cui
- , Di Liu
- & George F. Gao
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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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Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection
Antibiotics alter the intestinal microbiota and facilitate colonization of pathogens such as Clostridium difficile. Here, the authors show that antibiotic-induced shifts in the mouse gut microbiome are correlated with changes in levels of certain metabolites that C. difficilecan use for germination and growth.
- Casey M. Theriot
- , Mark J. Koenigsknecht
- & Vincent B. Young
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| Open AccessDrawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing
Adeno-associated viruses (AAV) are promising gene transfer vectors for human gene therapy. Here, the authors report a high-throughput, sequencing-based method for characterizing amino acid function in AAV capsids and highlight the potential of this method for improving capsid design.
- Kei Adachi
- , Tatsuji Enoki
- & Hiroyuki Nakai
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Programming a Pavlovian-like conditioning circuit in Escherichia coli
Synthetic gene circuits can be programmed in living cells to perform diverse cellular functions. Here, the authors program a genetic circuit that performs a Pavlovian-like learning and recall function in E. coli, and demonstrate the dynamic nature of this conditioning process at a population level.
- Haoqian Zhang
- , Min Lin
- & Qi Ouyang
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| Open AccessMultiple recent horizontal transfers of a large genomic region in cheese making fungi
Horizontal gene transfers are known to play an important role in prokaryote evolution but their impact and prevalence in eukaryotes is less clear. Here, the authors sequence the genomes of cheese making fungi P. roqueforti and P. camemberti, and provide evidence for recent horizontal transfers of a large genomic region.
- Kevin Cheeseman
- , Jeanne Ropars
- & Yves Brygoo
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Indoleamides are active against drug-resistant Mycobacterium tuberculosis
New classes of antitubercular drugs are in constant demand as drug-resistant strains of Mycobacterium tuberculosis become more prevalent. Here, the authors characterize a class of drugs that are active against various M. tuberculosisstrains, including those resistant to currently used antituberculars.
- Shichun Lun
- , Haidan Guo
- & William R. Bishai
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Effectors of animal and plant pathogens use a common domain to bind host phosphoinositides
Many Gram-negative bacterial pathogens use the type III secretion system to translocate effectors into the host cell. Here, the authors characterize a bacterial phosphoinositide-binding domain, which is conserved in diverse type III effectors of both plant and animal pathogens and couples membrane localization with refolding.
- Dor Salomon
- , Yirui Guo
- & Kim Orth
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HipA-mediated antibiotic persistence via phosphorylation of the glutamyl-tRNA-synthetase
Bacterial persistence is one of the major causes of failure of antibiotic treatment, and several toxin–antitoxin modules have been linked to the persistent phenotype. Here, the authors show that HipA toxin causes growth arrest and persistence via phosphorylation of the glutamyl-tRNA-synthetase.
- Ilana Kaspy
- , Eitan Rotem
- & Gad Glaser
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Multiparametric atomic force microscopy imaging of single bacteriophages extruding from living bacteria
Force-distance atomic force microscopy enables simultaneous recording of structure and biophysical properties at the nanoscale. Alsteens et al.combine this tool with tips that can recognise specific proteins, allowing them to image bacteriophages extruding from living bacteria.
- David Alsteens
- , Heykel Trabelsi
- & Yves F. Dufrêne
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A phenylalanine rotameric switch for signal-state control in bacterial chemoreceptors
Bacterial chemoreceptors regulate the kinase CheA via ligand-induced conformational changes. Using long molecular dynamics simulations, Ortega et al.show that these changes are associated with flipping of the stacked aromatic rings of highly conserved phenylalanine residues within the kinase-activating domain.
- Davi R. Ortega
- , Chen Yang
- & Igor B. Zhulin
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| Open AccessInfluenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
Some clinical isolates of influenza A(H7N9) virus encode a mutation within neuraminidase that could confer resistance to the only class of drugs active against H7N9. Here, the authors show that this mutation does not affect viral replication and pathogenicity while mediating resistance to antivirals in vivo.
- Rong Hai
- , Mirco Schmolke
- & Nicole M. Bouvier
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Supramolecular high-aspect ratio assemblies with strong antifungal activity
Efficient and pathogen-specific antifungal agents are required to mitigate drug resistance problems. Here the authors present a series of cationic small molecules, which are easy to isolate and characterize, and which can self-assemble to give polymer-like antifungal activity and specificity.
- Kazuki Fukushima
- , Shaoqiong Liu
- & James L. Hedrick
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Essential regulation of cell bioenergetics in Trypanosoma brucei by the mitochondrial calcium uniporter
The mitochondrial calcium uniporter supports oxidative phosphorylation in mammals; however, it is also present in blood-stage trypanosomes, which lack a functional respiratory chain. Huang et al. show that the mitochondrial calcium uniporter is essential for blood-stage survival and metabolism in Trypanosoma brucei.
- Guozhong Huang
- , Anibal E. Vercesi
- & Roberto Docampo
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| Open AccessMechanisms of molecular transport through the urea channel of Helicobacter pylori
Helicobacter pylori survives in the acidic environment of the stomach by taking up urea and converting it to ammonia and carbon dioxide, which buffer the bacterial periplasm. Using molecular dynamics simulations, McNulty et al. provide insight into the mechanism of urea uptake through the H. pyloriurea transporter.
- Reginald McNulty
- , Jakob P. Ulmschneider
- & Martin B. Ulmschneider
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Highly efficient methane biocatalysis revealed in a methanotrophic bacterium
Methane is a promising renewable carbon source for chemical synthesis, yet methane bio-gas is currently underutilised as a feedstock. Here the authors examine the metabolic processes of methanotrophic bacteria to assess their use for conversion of methane to value-added chemical products.
- M. G. Kalyuzhnaya
- , S. Yang
- & M. E. Lidstrom
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Discovery of chlamydial peptidoglycan reveals bacteria with murein sacculi but without FtsZ
Chlamydiae are sensitive to beta-lactam antibiotics, which target cell-wall peptidoglycan (PG), but it is unclear whether these bacteria possess PG. Pilhofer et al. now demonstrate that cell walls of a chlamydial species, Protochlamydia amoebophila, contain a PG layer.
- Martin Pilhofer
- , Karin Aistleitner
- & Grant J. Jensen
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| Open AccessTriggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum
Plasmodium falciparum reticulocyte-binding protein homologue 1 (PfRH1) and erythrocyte-binding-like protein EBA175 are important for parasite invasion of host cells. Here, Gao et al.show that PfRH1 activates calcium signalling, which induces release of EBA175 and allows junction formation between host cell and parasite.
- Xiaohong Gao
- , Karthigayan Gunalan
- & Peter R. Preiser
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Characterization and modelling of interspecies electron transfer mechanisms and microbial community dynamics of a syntrophic association
Microbial community function depends on metabolic interdependencies between individual species, some of which include electron transfer. Nagarajan et al. use genomic, transcriptomic and modelling approaches to describe the mechanisms supporting the syntrophic relationship between Geobacter metallireducens and Geobacter sulfurreducens.
- Harish Nagarajan
- , Mallory Embree
- & Karsten Zengler
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Continent-wide panmixia of an African fruit bat facilitates transmission of potentially zoonotic viruses
The African straw-coloured fruit bat lives in close proximity to humans and acts as reservoir for Lagos bat virus and henipaviruses. Here, the authors assess viral transmission dynamics in this species and its implications for public health using genetic and serological data.
- Alison J. Peel
- , David R. Sargan
- & Andrew A. Cunningham
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VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA
Toxin–antitoxin systems have been implicated in the pathogenicity of Mycobacterium tuberculosis. Here, the authors study the function of the M. tuberculosistoxin VapC20 and show that it can impair protein translation and inhibit bacterial growth by cleaving the Sarcin–Ricin loop of 23S rRNA
- Kristoffer S. Winther
- , Ditlev E. Brodersen
- & Kenn Gerdes
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A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection
Influenza virus can enter host cells through endocytosis, but the molecular pathways involved in this process are not fully understood. Here, the authors dissect these pathways and identify Ca2+as a key regulator of influenza A virus entry via both clathrin-mediated and clathrin-independent endocytosis.
- Yoichiro Fujioka
- , Masumi Tsuda
- & Yusuke Ohba
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Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase
SAMHD1 is a dNTP hydrolase that has been shown to act as a restriction factor against retroviruses such as HIV, and also regulates the retrotransposition of LINE-1 elements. Here the authors reveal the structural basis for dGTP-dependent tetramerization and allosteric activation of the enzyme.
- Chunfeng Zhu
- , Wenying Gao
- & Xiao-Fang Yu
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Chimeric viruses blur the borders between the major groups of eukaryotic single-stranded DNA viruses
Single-stranded DNA viruses are almost ubiquitous and highly diverse. Here, the authors focus on small DNA viruses possessing chimeric genomes with RNA virus-like capsids, disentangling their complex evolutionary history, which challenges the current borders between major groups of eukaryotic ssDNA viruses.
- Simon Roux
- , François Enault
- & Mart Krupovic
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Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides
Cytotoxic CD8+ T cells provide one level of protection against influenza infection. Here, the authors present evidence, in mice and humans, for the emergence and reversion of influenza A virus escape mutants associated with the immune pressure from cytotoxic CD8+ T lymphocytes.
- Sophie A. Valkenburg
- , Sergio Quiñones-Parra
- & Katherine Kedzierska
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Deoxygenation alters bacterial diversity and community composition in the ocean’s largest oxygen minimum zone
Oxygen minimum zones in the global ocean have an important role in biogeochemical cycles, yet their response to climate change is poorly understood. Here, the authors show that bacterial community composition is tightly coupled to dissolved oxygen and is likely to fundamentally change as the oceans warm.
- J. Michael Beman
- & Molly T. Carolan
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Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses
Mutations in the haemagglutinin of H5N1 avian influenza viruses confer transmissibility in ferrets. Here, Wilker et al. show that while within host variability is high, transmitted virus diversity is low suggesting a genetic bottleneck acts during transmission, driven by selection on haemagglutinin genes.
- Peter R. Wilker
- , Jorge M. Dinis
- & Thomas C. Friedrich
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| Open AccessHorizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers
Clostridium difficile produces potent toxins that are encoded by its pathogenicity locus. Here, Brouwer et al. demonstrate surprising bacterial genome plasticity whereby the pathogenicity locus is transferred from toxigenic to non-toxigenic strains of C. difficileby conjugational transfer.
- Michael S.M. Brouwer
- , Adam P. Roberts
- & Peter Mullany
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Evolutionary history predicts the stability of cooperation in microbial communities
Persistence of cooperation requires limited spread of defectors, but it is unclear how evolutionary history affects the spread of these individuals. Here, Jousset et al.show that microbial cooperators can only inhibit defectors that are closely related to them, suggesting that evolutionary history can predict the stability of cooperation.
- Alexandre Jousset
- , Nico Eisenhauer
- & Stefan Scheu
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Structure of GrlR–GrlA complex that prevents GrlA activation of virulence genes
The locus of enterocyte effacement is a pathogenicity island essential for virulence of some Escherichia colipathogenic serotypes. Here, the authors solve the structure of a regulatory complex that optimizes regulation of this locus during the infection process.
- Abhilash Padavannil
- , Chacko Jobichen
- & J. Sivaraman
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| Open AccessThe landscape of viral expression and host gene fusion and adaptation in human cancer
Viruses contribute to the pathogenesis of certain cancers. Using massively parallel sequencing data from The Cancer Genome Atlas to analyse viral expression in 19 tumour types, Tang et al. both confirm and reject previously described viral associations and present new information on viral integration and host interaction.
- Ka-Wei Tang
- , Babak Alaei-Mahabadi
- & Erik Larsson
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Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity
Tempol is an antioxidant that reduces the body weight of mice on a high-fat diet. Li et al.now provide a mechanistic link by demonstrating that tempol affects the intestinal microbiota, which leads to a change in the composition of bile acids and suppression of FXR signalling.
- Fei Li
- , Changtao Jiang
- & Frank J. Gonzalez
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Implementation of stable and complex biological systems through recombinase-assisted genome engineering
Genetic engineering of bacteria is an important tool in biotechnology and synthetic biology. Here, the authors describe a method for genomic integration of complex, multi-gene sequences into bacteria and use it to create a strain of E. colithat generates ethanol from brown macroalgae.
- Christine Nicole S. Santos
- , Drew D. Regitsky
- & Yasuo Yoshikuni
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| Open AccessStructure of a helicase–helicase loader complex reveals insights into the mechanism of bacterial primosome assembly
During the initiation of bacterial DNA replication, loader proteins transfer the hexameric helicase ring onto replication origin DNA. Liu et al.report the crystal structure of a 570-kDa prepriming complex and suggest that the release of loader proteins is associated with the transition of the helicase ring to a spiral configuration.
- Bin Liu
- , William K. Eliason
- & Thomas A. Steitz
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Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria
Bacterial cell division requires the coordination of chromosome replication with cell growth and division but how these processes are coordinated in mycobacteria is largely unexplored. Santi et al. use single-cell technologies to describe the cell cycle dynamics of Mycobacterium smegmatisand outline important differences in comparison with other bacterial species.
- Isabella Santi
- , Neeraj Dhar
- & John D. McKinney
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| Open AccessGenome signature-based dissection of human gut metagenomes to extract subliminal viral sequences
Bacteriophages have a significant impact on microbial ecosystems, but additional tools are needed to assess viral communities. Ogilvie et al.present a new strategy to extract viral sequences from metagenomic data sets, and present new insights on their function in the gut ecosystem.
- Lesley A. Ogilvie
- , Lucas D. Bowler
- & Brian V. Jones
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Advection shapes Southern Ocean microbial assemblages independent of distance and environment effects
Environmental factors and distance are known to influence the structure of marine microbial communities. Using a data set spanning the Southern Ocean, Wilkins et al.now demonstrate that fluid transport (advection) is another important factor involved in shaping the marine microbial ecosystem.
- David Wilkins
- , Erik van Sebille
- & Ricardo Cavicchioli
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| Open AccessHuman gut microbiota community structures in urban and rural populations in Russia
The structure of the human gut microbiota has been shown to vary between populations. Tyakht et al.analyse the gut microbiota assembly from Russian individuals living in urban and rural areas, and compare these with previously studied populations.
- Alexander V. Tyakht
- , Elena S. Kostryukova
- & Vadim M. Govorun
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Social amoeba farmers carry defensive symbionts to protect and privatize their crops
The social amoeba Dictyostelium discoideum displays a primitive form of agriculture with some clones carrying bacteria to seed out food crops. Brock et al. now demonstrate that these farmers also carry non-food bacteria that harm competing non-farmer amoeba clones, protecting the crop from exploitation.
- Debra A. Brock
- , Silven Read
- & Joan E. Strassmann
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