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| Open AccessBiochemical mechanisms determine the functional compatibility of heterologous genes
Sequence composition is thought to be a major factor governing the functionality of horizontally transferred genes. In contrast, Porse et al. show that phylogenetic origin, and the type of resistance mechanism, are major factors affecting the functionality of horizontally transferred antibiotic resistance genes.
- Andreas Porse
- , Thea S. Schou
- & Morten O. A. Sommer
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Article
| Open AccessSensory deprivation in Staphylococcus aureus
Bacteria use two-component systems (TCSs) to sense and respond to environmental changes. Here, the authors show that Staphylococcus aureus can survive in the absence of all its 16 TCSs under growth arrest conditions, and each TCS seems to be sufficient to sense and respond to specific environmental clues.
- Maite Villanueva
- , Begoña García
- & Iñigo Lasa
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| Open AccessGlobal role of the bacterial post-transcriptional regulator CsrA revealed by integrated transcriptomics
The RNA-binding protein CsrA regulates the expression of hundreds of bacterial genes. Here, Potts et al. use several approaches to assess the contribution of CsrA to global gene expression in E. coli, revealing new binding targets and physiological roles such as in envelope function and iron homeostasis.
- Anastasia H. Potts
- , Christopher A. Vakulskas
- & Tony Romeo
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| Open AccessThe multiple antibiotic resistance operon of enteric bacteria controls DNA repair and outer membrane integrity
Transcription factors MarR and MarA confer multidrug resistance in enteric bacteria by modulating efflux pump and porin expression. Here, Sharma et al. show that MarA also upregulates genes required for lipid trafficking and DNA repair, thus reducing antibiotic entry and quinolone-induced DNA damage.
- Prateek Sharma
- , James R. J. Haycocks
- & David C. Grainger
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| Open AccessA comprehensive characterization of PncA polymorphisms that confer resistance to pyrazinamide
The antibiotic pyrazinamide is central to tuberculosis treatment regimens, globally. Despite its efficacy, resistance to the drug is increasing. Here, Eric Rubin and colleagues characterise the genetic basis of pyrazinamide resistance.
- Adam N. Yadon
- , Kashmeel Maharaj
- & Alexander S. Pym
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| Open AccessThe Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation
Cas5 is a transcriptional regulator of responses to cell wall stress in the fungal pathogen Candida albicans. Here, Xie et al. show that Cas5 also modulates cell cycle dynamics and responses to antifungal drugs.
- Jinglin L. Xie
- , Longguang Qin
- & Leah E. Cowen
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Article
| Open AccessLong-term genomic coevolution of host-parasite interaction in the natural environment
Arms races between phage and bacteria are well known from lab experiments, but insight from field systems is limited. Here, the authors show changes in the resistance and CRISPR loci of bacteria and the infectivity, host range and genome size of phage over multiple years in an aquaculture environment.
- Elina Laanto
- , Ville Hoikkala
- & Lotta-Riina Sundberg
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Article
| Open AccessZinc-dependent regulation of zinc import and export genes by Zur
Zinc homeostasis in most bacteria is achieved by a set of regulators, each responding to a certain level of intracellular zinc. Here the authors show that, inStreptomyces coelicolor, the Zur regulator modulates the expression of genes for zinc import and export over a large range of zinc concentrations.
- Seung-Hwan Choi
- , Kang-Lok Lee
- & Jung-Hye Roe
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Article
| Open AccessDissemination of antibiotic resistance genes from antibiotic producers to pathogens
Some antibiotic resistance genes found in pathogenic bacteria might derive from antibiotic-producing actinobacteria. Here, Jianget al. provide bioinformatic and experimental evidence supporting this hypothesis, and propose a specific mechanism for the transfer of these genes between bacterial phyla.
- Xinglin Jiang
- , Mostafa M. Hashim Ellabaan
- & Sang Yup Lee
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Article
| Open AccessMetabolic network analysis reveals microbial community interactions in anammox granules
The use of anammox microbiomes to treat wastewater is an escalating biotechnology, yet the functional role heterotrophic bacteria play in these systems remains poorly understood. Here, Lawsonet al. use metagenomics and metatranscriptomics to reveal that heterotrophs degrade free peptides, while recycling nitrate to nitrite.
- Christopher E. Lawson
- , Sha Wu
- & Daniel R. Noguera
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Article
| Open AccessEvolutionary dynamics and genomic features of the Elizabethkingia anophelis 2015 to 2016 Wisconsin outbreak strain
Elizabethkingia anophelis is an emerging pathogen of high antimicrobial resistance. Perrin and colleagues sequenced isolates of a 2015/2016 E. anophelis outbreak in Wisconsin and found substantial genetic diversity, accelerated evolutionary rate and a disruptive mutation in the DNA repair gene mutY.
- Amandine Perrin
- , Elise Larsonneur
- & Sylvain Brisse
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Article
| Open AccessDetermining the bacterial cell biology of Planctomycetes
Several unusual features have been reported for bacteria of the phylum Planctomycetes, such as cytosolic compartmentalization and an endocytosis-like process. Here, Boedekeret al. provide evidence supporting a Gram-negative cell plan and the absence of endocytosis-like processes in these organisms.
- Christian Boedeker
- , Margarete Schüler
- & Christian Jogler
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Article
| Open AccessManagement of E. coli sister chromatid cohesion in response to genotoxic stress
Homologous recombination of DNA lesions in bacteria involves sister chromatid pairing. Here, the authors show that RecN promotes contacts between sister chromatids and facilitates repair.
- Elise Vickridge
- , Charlene Planchenault
- & Olivier Espéli
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| Open AccessA non-canonical mismatch repair pathway in prokaryotes
Despite the importance of mismatch repair for genome stability, many Archaea and almost all Actinobacteria lack MutS and MutL proteins. Here the authors, usingMycobacterium smegmatisas a model, report that NucS/EndoMS endonuclease acts in a distinct mismatch repair pathway.
- A. Castañeda-García
- , A. I. Prieto
- & J. Blázquez
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| Open AccessGlobal and local selection acting on the pathogen Stenotrophomonas maltophilia in the human lung
The authors sequence the genomes of 552 bacterial isolates sampled across 23 sites of the lungs of a patient with cystic fibrosis, and identify bacterial genes under global and location-specific adaptation.
- Hattie Chung
- , Tami D. Lieberman
- & Roy Kishony
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| Open AccessGlobal repositioning of transcription start sites in a plant-fermenting bacterium
Bacteria may respond to a change in environment by using alternative transcriptional start sites. Here, the authors use a novel genome-wide capture and reverse transcription method to find substrate-specific start sites for hundreds of genes at single base resolution inClostridium phytofermentans.
- Magali Boutard
- , Laurence Ettwiller
- & Andrew C. Tolonen
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Article
| Open AccessChaperone addiction of toxin–antitoxin systems
Some bacterial toxin-antitoxin systems consist of a labile antitoxin that inhibits a toxin, and a chaperone that stabilizes the antitoxin. Here, Bordes et al. identify a sequence within the antitoxin to which the chaperone binds and which can be transferred to other proteins to make them chaperone-dependent.
- Patricia Bordes
- , Ambre Julie Sala
- & Pierre Genevaux
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Article
| Open AccessAn extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid
Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi). This study examines ∼2,000 clinical isolates of S. Typhi to show highly structured/geographically restricted genomes except rapidly disseminating H58 subclade, and design a genotyping framework for tracking the disease.
- Vanessa K. Wong
- , Stephen Baker
- & Ben Amos
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| Open AccessThe evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions
Colistin is an antibiotic used in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis patients. Here, Jochumsen et al. reconstruct the pathways for the molecular evolution of colistin resistance in P. aeruginosaand show that the number of pathways is highly constrained by interactions among genes.
- Nicholas Jochumsen
- , Rasmus L. Marvig
- & Anders Folkesson
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| Open AccessSequence element enrichment analysis to determine the genetic basis of bacterial phenotypes
Plasticity and clonal population structure in bacterial genomes can hinder traditional SNP-based genetic association studies. Here, Corander and colleagues present a method to identify variable-length sequence elements enriched in a phenotype of interest, and demonstrate its use in human pathogens.
- John A. Lees
- , Minna Vehkala
- & Jukka Corander
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| Open AccessMolecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis
The transcription factor Zur controls the zinc deprivation response in Bacillus subtilis. Here, Shin and Helmann show that Zur-regulated genes are derepressed in three waves in response to zinc deprivation, and this is linked to the biochemistry of zinc sensing by Zur.
- Jung-Ho Shin
- & John D. Helmann
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Article
| Open AccessA rheostat mechanism governs the bifurcation of carbon flux in mycobacteria
Microbes survive in dynamic environments by modulating their intracellular metabolism. Here, the authors reveal that mycobacteria employ a rheostat-like mechanism to regulate carbon flux between the oxidative TCA cycle and the glyoxylate shunt during glucose-acetate diauxic shift.
- Paul Murima
- , Michael Zimmermann
- & John D. McKinney
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| Open AccessAn integrated genomic and transcriptomic survey of mucormycosis-causing fungi
Fungi of the order Mucorales can cause life-threatening infections. Here, Chibucos et al. present genomic and transcriptomic analyses of a diverse set of Mucorales fungi, shedding light on their evolution and identifying potential therapeutic targets in the pathogens and the host.
- Marcus C. Chibucos
- , Sameh Soliman
- & Vincent M. Bruno
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Article
| Open AccessGenome-wide analysis of chromosomal import patterns after natural transformation of Helicobacter pylori
Uptake and integration of exogenous DNA into the bacterial genome play an important role in the evolution of the pathogen Helicobacter pylori. Here, the authors describe a bimodal pattern of chromosomal integration and show how restriction-modification systems limit the import of heterologous DNA.
- Sebastian Bubendorfer
- , Juliane Krebes
- & Sebastian Suerbaum
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| Open AccessThe dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2)
Bacteria of the genus Streptomyces produce a great variety of natural products, the biosynthesis of which is subject to complex regulatory networks. Here the authors present a high-resolution, genome-wide analysis of the transcriptome and translatome of Streptomyces coelicolorunder various growth conditions.
- Yujin Jeong
- , Ji-Nu Kim
- & Byung-Kwan Cho
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Article
| Open AccessHsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans
The transcription factor Hsf1 and the molecular chaperone Hsp90 modulate the heat shock response in the pathogen Candida albicans. Here, Leach et al. reveal a complex interplay between the two factors that regulates the expression of genes involved in the heat shock response and virulence.
- Michelle D. Leach
- , Rhys A. Farrer
- & Leah E. Cowen
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Article
| Open AccessExperimental evolution reveals that high relatedness protects multicellular cooperation from cheaters
Maintenance of cooperation in multicellular organisms is hypothesized to depend on high relatedness among cells. Here, Bastiaans et al. provide empirical support for this hypothesis by directly comparing the evolutionary stability of multicellular cooperation in experimental lines of a fungus kept at either high or low relatedness.
- Eric Bastiaans
- , Alfons J. M. Debets
- & Duur K. Aanen
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Article
| Open AccessGenome-based microbial ecology of anammox granules in a full-scale wastewater treatment system
ANaerobic AMMonium OXidation (ANAMMOX) combined with partial nitritation has been adopted for removal of ammonium from wastewater. Here, Speth et al. describe the bacterial metagenome of a partial-nitritation/anammox (PNA) reactor, and provide 23 draft genomes, 19 of which were previously uncharacterized/sequenced/cultivated.
- Daan R. Speth
- , Michiel H. in ’t Zandt
- & Mike S. M. Jetten
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Article
| Open AccessPrevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance
The fungal pathogen Candida glabrata readily acquires resistance to multiple types of antifungal drugs. Here, Healey et al. show that C. glabrataclinical isolates often carry mutations in a gene involved in DNA mismatch repair, and this is associated with increased propensity to develop antifungal resistance.
- Kelley R. Healey
- , Yanan Zhao
- & David S. Perlin
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Article
| Open AccessMajor bacterial lineages are essentially devoid of CRISPR-Cas viral defence systems
It is thought that CRISPR-Cas systems, which confer acquired immunity to phage and archaeal viruses, are widespread among bacteria and archaea. Here, Burstein et al.show that entire lineages of uncultivated microorganisms are essentially devoid of CRISPR-Cas systems.
- David Burstein
- , Christine L. Sun
- & Jillian F. Banfield
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Article
| Open AccessRapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis
The clinical application of new sequencing techniques is expected to accelerate pathogen identification. Here, Bradley et al. present a clinician-friendly software package that uses sequencing data for quick and accurate prediction of antibiotic resistance profiles for S. aureus and M. tuberculosis.
- Phelim Bradley
- , N. Claire Gordon
- & Zamin Iqbal
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Article
| Open AccessAdaptive immunity increases the pace and predictability of evolutionary change in commensal gut bacteria
The mechanisms underlying host-commensal coevolution are incompletely understood. Here the authors show that host adaptive immunity directs the evolution of Escherichia coliin the mouse gut towards host benefit by influencing the microbiome composition.
- João Barroso-Batista
- , Jocelyne Demengeot
- & Isabel Gordo
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Article
| Open AccessGenetic interactions contribute less than additive effects to quantitative trait variation in yeast
This study uses a large number of crosses between a common lab strain and vineyard-isolated strain of yeast, and estimates the phenotypic variance for various quantitative traits. Using this data set, the authors show additive quantitative trait loci (QTL) and QTL–QTL interactions to be on average 43% and 9%, respectively.
- Joshua S. Bloom
- , Iulia Kotenko
- & Leonid Kruglyak
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Article
| Open AccessAllelic variation contributes to bacterial host specificity
One of the key aspects for controlling infectious diseases is understanding how pathogens cross host species. Here the authors conduct a genome-wide analysis of Salmonella and show a high degree of variation, enabling host-adapted colonization among Salmonellaintestinal and systemic serovars.
- Min Yue
- , Xiangan Han
- & Dieter M. Schifferli
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Article
| Open AccessThe external domains of the HIV-1 envelope are a mutational cold spot
Mutations allow RNA virus to adapt fast but also entail fitness costs. Geller et al. show that, in HIV-1, mutations occur three times less often in the most external domains of the envelope, and that this is due to changes in RNA sequence context and structure, which control viral and host-encoded mutational mechanisms.
- Ron Geller
- , Pilar Domingo-Calap
- & Rafael Sanjuán
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| Open AccessStructure of Ljungan virus provides insight into genome packaging of this picornavirus
The Ljungan virus is a picornavirus that lacks the internal coat protein VP4, and the packaging of its RNA genome is poorly understood. Here, the authors use cryo-electron microscopy to visualize this virus and suggest that it uses a different mechanism to other viruses for encapsidation of its genome.
- Ling Zhu
- , Xiangxi Wang
- & David I. Stuart
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| Open AccessExpanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera
Lactobacillus is a lactic acid bacteria and has a wide range of application from use in probiotic food production to biotherapeutics. Here, the authors sequence and compare the genomes of 213 different Lactobacillusstrains and related genera, and provide new insight into phylogenomic organization and adaptive immunity elements in this bacteria family.
- Zhihong Sun
- , Hugh M. B. Harris
- & Paul W. O’Toole
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Article
| Open AccessConvergent capture of retroviral superantigens by mammalian herpesviruses
Horizontal gene transfer from retroviruses to mammals is rare between unrelated viruses. Here the authors show the convergent acquisition by herpesviruses of a virulence gene of ancient retroviruses, which occurred at least twice from different donor lineages, to distinct herpesviruses that infect mammals.
- Amr Aswad
- & Aris Katzourakis
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Article
| Open AccessA biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae
Non-typeable Haemophilus influenzae, which causes ear and lung infections, has a DNA methyltransferase encoded by alternative alleles that are subject to random ON/OFF switching. Here, Atack et al.show that this epigenetic switch controls the expression of key proteins involved in virulence.
- John M. Atack
- , Yogitha N. Srikhanta
- & Michael P. Jennings
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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 AccessIdentification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus
Understanding the factors that enable some bird flu viruses to infect humans is important for the identification of circulating viruses with higher potential to infect us. Here, Taft et al.identify novel mutations in the polymerase of an avian H5N1 virus that help the virus to replicate in human cells and in mice
- Andrew S. Taft
- , Makoto Ozawa
- & Yoshihiro Kawaoka
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Article
| Open AccessSingle molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes
Bacterial DNA methylation is involved in many processes, from host defense to antibiotic resistance, however current methods for examining methylated genomes lack single-cell resolution. Here Beaulaurier et al. present Single Molecule Modification Analysis of Long Reads, a new tool for de novodetection of epigenetic heterogeneity.
- John Beaulaurier
- , Xue-Song Zhang
- & Gang Fang
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Article
| Open AccessPhasing of single DNA molecules by massively parallel barcoding
DNA phasing information — the determination of which specific sequences belong to the same DNA molecule—is not easily obtained from sequencing applications that rely on short reads. Here the authors develop a phasing method based on massively parallel barcoding of single DNA molecules.
- Erik Borgström
- , David Redin
- & Afshin Ahmadian
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Article
| Open AccessCharacterization of genome-wide ordered sequence-tagged Mycobacterium mutant libraries by Cartesian Pooling-Coordinate Sequencing
The generation of characterized panels of specific mutants is an essential but time-consuming step of reverse genetic studies. Here Vandewalle et al. describe CP-CSeq, an easy to implement parallel sequencing method for rapid library construction.
- Kristof Vandewalle
- , Nele Festjens
- & Nico Callewaert
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Article
| Open AccessInteractions between horizontally acquired genes create a fitness cost in Pseudomonas aeruginosa
Horizontal gene transfer is important for bacterial evolution but the molecular basis of its fitness costs remain unclear. Here the authors show that fitness costs produced by a plasmid in P. aeruginosaare alleviated by mutations in recently acquired genes encoded in mobile genetic elements.
- Alvaro San Millan
- , Macarena Toll-Riera
- & R. Craig MacLean
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Article
| Open AccessGlobal analysis of fungal morphology exposes mechanisms of host cell escape
Several pathogenic fungi such as Candida albicans undergo transitions between single-celled forms and multicellular filaments. Here the authors perform a genome-scale analysis of C. albicansand show that, contrary to common belief, filamentation is not required for escape from host immune cells.
- Teresa R. O’Meara
- , Amanda O. Veri
- & Leah E. Cowen
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Article
| Open AccessGenomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis
The bacterium Streptococcus suiscauses respiratory tract infections in pigs and meningitis in humans. Here, the authors show that human disease isolates are limited to a single virulent population and find no consistent genomic differences between pig and human isolates.
- Lucy A. Weinert
- , Roy R. Chaudhuri
- & Vanessa Terra
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Article
| Open AccessTargeted diversity generation by intraterrestrial archaea and archaeal viruses
Diversity-generating retroelements (DGRs) are genetic elements that introduce sequence variation within target genes in bacteria and their viruses. Here, Paul et al. report the discovery of DGRs in an archaeal virus and in two archaea from marine and terrestrial subsurface environments, respectively.
- Blair G. Paul
- , Sarah C. Bagby
- & David L. Valentine
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Article |
The 40-residue insertion in Vibrio cholerae FadR facilitates binding of an additional fatty acyl-CoA ligand
FadR is a regulator of fatty acid metabolism in bacteria, and contains a binding site for acyl-CoA. Here, Shi et al. present a structure of V. cholerae FadR and show that a unique C-terminal extension comprises a second acyl-CoA binding site, perhaps rendering V. choleraeFadR a more efficient regulator.
- Wei Shi
- , Gabriela Kovacikova
- & F. Jon Kull