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| Open AccessEarly emergence of Yersinia pestis as a severe respiratory pathogen
Yersinia pestis, which evolved from a gastrointestinal pathogen, causes pneumonic and bubonic plague. Here Zimbler et al. show that the gain of a single protein enabled Y. pestisto first cause pneumonic plague, and one amino-acid change in the same protein then allowed the bacteria to efficiently cause bubonic plague.
- Daniel L. Zimbler
- , Jay A. Schroeder
- & Wyndham W. Lathem
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Article
| Open AccessGlycan complexity dictates microbial resource allocation in the large intestine
The human gut microbiota helps us to degrade complex dietary carbohydrates such as xylan and, in turn, the carbohydrate breakdown products control the structure of the microbiota. Here the authors characterize the xylan-degrading apparatus of a key member of the gut microbiota, Bacteroides ovatus.
- Artur Rogowski
- , Jonathon A. Briggs
- & David N. Bolam
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Article
| Open AccessCaenorhabditis elegans is a useful model for anthelmintic discovery
Screening for new anthelmintic compounds that are active against parasitic nematodes is costly and labour intensive. Here, the authors use the non-parasitic nematode Caenorhabditis elegansto identify 30 anthelmintic lead compounds in an effective and cost-efficient manner.
- Andrew R. Burns
- , Genna M. Luciani
- & Peter J. Roy
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Article
| Open AccessLucilia cuprina genome unlocks parasitic fly biology to underpin future interventions
Lucilia cuprina is a parasitic blowfly of major economic importance worldwide that feeds on the tissues of animals such as sheep. Here, the authors sequence the genome of L. cuprinaand provide insights into the fly’s molecular biology, interactions with the host animal and insecticide resistance.
- Clare A. Anstead
- , Pasi K. Korhonen
- & Robin B. Gasser
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Article
| Open AccessIL-21 induces antiviral microRNA-29 in CD4 T cells to limit HIV-1 infection
HIV-infected patients who maintain undetectable virus levels possess elevated plasma concentrations of IL-21. Here, Adoroet al. show that IL-21 inhibits early viral infection in humanized mice and suppresses HIV-1 replication in vitroby upregulating a microRNA via the regulatory protein STAT3.
- Stanley Adoro
- , Juan R. Cubillos-Ruiz
- & Laurie H. Glimcher
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Article
| Open AccessTwo-dimensional isobutyl acetate production pathways to improve carbon yield
Achieving high carbon yields is crucial for biotechnological production of metabolites in engineered microorganisms. Here, Tashiroet al. generate E. colistrains that produce acetyl-CoA and a derived metabolite (isobutyl acetate) in the absence of pyruvate decarboxylation, leading to increased carbon yields.
- Yohei Tashiro
- , Shuchi H. Desai
- & Shota Atsumi
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Article
| Open AccessThe immunomodulating V and W proteins of Nipah virus determine disease course
Nipah virus (NiV) can be transmitted from bats and other animals to humans, causing severe encephalitis and respiratory disease. Here, Satterfield et al.show that the W protein of NiV modulates the host immune response and determines disease course in a ferret model of infection.
- Benjamin A. Satterfield
- , Robert W. Cross
- & Chad E. Mire
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Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies
The glycan patch that covers the HIV-1 envelope protein gp120 can be targeted by broadly neutralizing antibodies. Here, Pritchard et al.show that structural changes in the glycans do not significantly hamper antibody recognition, supporting the glycan patch as a stable target for vaccine design.
- Laura K. Pritchard
- , Daniel I.R. Spencer
- & Max Crispin
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The bacterial tubulin FtsZ requires its intrinsically disordered linker to direct robust cell wall construction
The bacterial division protein FtsZ recruits cell wall synthesis enzymes to the cytokinetic ring. Sundararajan et al.show that FtsZ deletion variants alter peptidoglycan structure without detectable effects on enzyme recruitment, suggesting an additional role in the regulation of cell wall metabolism.
- Kousik Sundararajan
- , Amanda Miguel
- & Erin D. Goley
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Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites
Growing evidence suggests that environmental rather than genetic factors are major contributors to asthma development. Here the authors show that high intake of dietary fibre by pregnant mice increases resistance of their progeny to the development of allergic airways disease.
- Alison N. Thorburn
- , Craig I. McKenzie
- & Charles R. Mackay
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Inefficient microbial production of refractory dissolved organic matter in the ocean
The extent to which the microbial carbon pump contributes to the generation of marine refractory dissolved organic matter (RDOM) remains a matter of debate. Here, the authors report results from a 3-year mesocosm study, and show that most of the microbial DOM is different from RDOM in the ocean.
- Helena Osterholz
- , Jutta Niggemann
- & Thorsten Dittmar
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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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| 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 AccessAAV-mediated in vivo functional selection of tissue-protective factors against ischaemia
Cell-based screening assays allow functional testing of chemicals but do not mimic the in vivosituation well. Here, the authors report a method for the discovery of secreted cytoprotective factors in mice and use it to demonstrate that the hormone ghrelin protects cardiac muscle from ischaemic damage.
- Giulia Ruozi
- , Francesca Bortolotti
- & Mauro Giacca
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Delayed commitment to evolutionary fate in antibiotic resistance fitness landscapes
Antibiotic resistance can evolve through the stepwise accumulation of mutations. Here, the authors reconstruct the multistep evolutionary pathway for trimethoprim resistance and show that epistatic interactions increase rather than decrease the accessibility of each adaptive peak.
- Adam C. Palmer
- , Erdal Toprak
- & Roy Kishony
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HIV-1 Rev downregulates Tat expression and viral replication via modulation of NAD(P)H:quinine oxidoreductase 1 (NQO1)
Tat and Rev are HIV-1 proteins involved in feedback mechanisms that regulate the expression of viral genes. Here, the authors show that Rev reduces the intracellular Tat levels by inhibiting the expression of the cellular protein NQO1, which prevents Tat degradation.
- Sneh Lata
- , Amjad Ali
- & Akhil C. Banerjea
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Article
| Open AccessSite-specific processing of Ras and Rap1 Switch I by a MARTX toxin effector domain
V. vulnificus, a bacteria that cause life-threatening septicaemia following wound infections or tainted food consumption, utilizes MARTX toxins for toxic effector delivery. Here the authors show that the MARTX virulence factor DUF5 targets the cellular MAP kinase pathway as a Ras and Rap1 site-specific protease.
- Irena Antic
- , Marco Biancucci
- & Karla J. F. Satchell
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| Open AccessMultiparametric AFM reveals turgor-responsive net-like peptidoglycan architecture in live streptococci
The peptidoglycan (PG) layer of the Gram-positive bacteria cell wall resists turgor pressure, but the architecture of this layer is largely unknown. Here the authors use high resolution atomic force microscopy to image the PG layer from live Streptococcusto reveal a net-like arrangement that resists osmotic challenge by stretching and stiffening.
- Ron Saar Dover
- , Arkady Bitler
- & Yechiel Shai
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| Open AccessA common assembly module in injectisome and flagellar type III secretion sorting platforms
In bacteria, type III secretion systems (T3SS) allow the direct transport of protein across membranes, and related elements of a sorting platform facilitate hierarchical secretion of protein substrates. Here, the authors illustrate the mechanism of selective assembly of the T3SS sorting platforms in injectisome and flagellar systems.
- Ryan Q. Notti
- , Shibani Bhattacharya
- & C. Erec Stebbins
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Article
| Open AccessWidespread disruption of host transcription termination in HSV-1 infection
Herpes simplex virus 1 (HSV-1) efficiently shuts down host gene expression in infected cells. Here Rutkowski et al. analyse the genome-wide changes in transcription and translation in infected cells, and show that HSV-1 triggers an extensive disruption of transcription termination of cellular genes.
- Andrzej J. Rutkowski
- , Florian Erhard
- & Lars Dölken
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| Open AccessIntestinal intraepithelial lymphocyte activation promotes innate antiviral resistance
Intraepithelial lymphocytes in the gut eliminate dysfunctional epithelial cells and promote regrowth of healthy cells. Here the authors show that, in addition, these lymphocytes protect cells against viral infections by rapidly activating interferon-dependent pathways in intestinal epithelial cells.
- Mahima Swamy
- , Lucie Abeler-Dörner
- & Adrian C. Hayday
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Article
| Open AccessContrasting host–pathogen interactions and genome evolution in two generalist and specialist microsporidian pathogens of mosquitoes
Microsporidia are intracellular parasitic fungi that infect diverse animal hosts including humans. Here, Desjardins et al.present genomic and transcriptomic data for two microsporidia that infect disease-transmitting mosquitoes, highlighting differences in potential host interplay mechanisms.
- Christopher A. Desjardins
- , Neil D. Sanscrainte
- & Christina A Cuomo
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Article
| Open AccessRecovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8+ T cells
H7N9 avian influenza viruses can cause severe human disease. Here, the authors analyse blood samples from hospitalized H7N9 patients and show that a diversity of immune mechanisms seem to influence disease length and outcome.
- Zhongfang Wang
- , Yanmin Wan
- & Jianqing Xu
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Article
| Open AccessAnammox Planctomycetes have a peptidoglycan cell wall
Planctomycetes are unusual bacteria with complex intracellular compartments and an apparent lack of peptidoglycan in their cell walls. Here, van Teeseling et al. show that the cell wall of an anammox planctomycete does contain peptidoglycan, and propose to redefine planctomycetes as Gram-negative bacteria.
- Muriel C.F. van Teeseling
- , Rob J. Mesman
- & Laura van Niftrik
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Article
| Open AccessPlanctomycetes do possess a peptidoglycan cell wall
Planctomycetes appear to differ from all other bacteria in their cellular organization and their apparent lack of a peptidoglycan (PG) cell wall. Here Jeske et al. show that Planctomycetes do possess a typical PG cell wall and that their cellular architecture resembles that of Gram-negative bacteria.
- Olga Jeske
- , Margarete Schüler
- & Christian Jogler
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Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut
Gut inflammation triggers a bloom of certain resident bacteria such as E. coli that can contribute to disease. Here, Singh et al. show that a siderophore produced by E. coliinhibits the antibacterial activity of host myeloperoxidase and enhances bacterial survival in the gut of lab mice.
- Vishal Singh
- , Beng San Yeoh
- & Matam Vijay-Kumar
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Article
| Open AccessFour decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain
The early origin and evolution of multidrug resistant strains of Mycobacterium tuberculosisare poorly understood. Here, the authors perform genomic and phylogenetic analyses of 252 clinical isolates from a tuberculosis outbreak in Argentina and reconstruct the timeline of the acquisition of antibiotic resistance.
- Vegard Eldholm
- , Johana Monteserin
- & Francois Balloux
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| 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 AccessTopological control of the Caulobacter cell cycle circuitry by a polarized single-domain PAS protein
The bacterium Caulobacter crescentus is a model organism for research on the bacterial cell cycle and cell division processes. Here, Sanselicio et al. show that the MopJ protein contributes to the control of cell cycle and growth in C. crescentus.
- Stefano Sanselicio
- , Matthieu Bergé
- & Patrick H. Viollier
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Article
| Open AccessExpression of heterologous sigma factors enables functional screening of metagenomic and heterologous genomic libraries
Screening genomic or metagenomic libraries for interesting products or activities is often hampered by poor gene expression in a heterologous host. Here the authors show that the expression of a Lactobacillus sigma factor greatly enhances transcription of heterologous and environmental DNA in E. coli.
- Stefan M. Gaida
- , Nicholas R. Sandoval
- & Eleftherios T. Papoutsakis
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Heparanase is a host enzyme required for herpes simplex virus-1 release from cells
Herpesviruses bind to heparan sulphate (HS) on the surface of cells before infecting them. Here, the authors show that heparanase, a host enzyme that degrades HS and is upregulated on viral infection, is required for the release of newly formed viruses from infected cells.
- Satvik R. Hadigal
- , Alex M. Agelidis
- & Deepak Shukla
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Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis
Microbial and host cells in the gut exchange complex signals that we only begin to decipher. Here the authors show that pathogenic but not commensal gut bacteria secrete microparticles, which in turn induce changes in the content of the mucosa-produced exosomes to promote Th17-mediated tumorigenesis.
- Zhongbin Deng
- , Jingyao Mu
- & Huang-Ge Zhang
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Article
| Open AccessCellulosome stoichiometry in Clostridium cellulolyticum is regulated by selective RNA processing and stabilization
Selective RNA processing and stabilization (SRPS) can regulate bacterial operons, but the process is not well understood. Here, the authors show that the stoichiometry of cellulosome, a 12-subunit protein complex expressed from an operon in Gram-positive Clostridium cellullolyticum, is regulated by SRPS.
- Chenggang Xu
- , Ranran Huang
- & Jian Xu
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Article
| Open AccessDeoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria
Fluoroquinolone antibiotics are widely used to treat serious bacterial infections, but resistance is an increasing problem. Here the authors describe the synthesis and characterization of novel deoxynybomycin derivatives that exhibit activity against fluoroquinolone-resistant infections in an in vivomodel.
- Elizabeth I. Parkinson
- , Joseph S. Bair
- & Paul J. Hergenrother
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In vitro transport activity of the fully assembled MexAB-OprM efflux pump from Pseudomonas aeruginosa
Tripartite multidrug efflux pumps are important determinants of antibiotic resistance in several pathogenic bacteria. Here Verchère et al. design an in vitro assay system to study the transport properties of the MexAB-OprM efflux pump from Pseudomonas aeruginosa.
- Alice Verchère
- , Manuela Dezi
- & Martin Picard
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Article
| Open AccessASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction
The human protein APOBEC3G (A3G) inhibits HIV-1 replication, but the viral protein Vif counteracts by inducing A3G degradation. Here Miyakawa et al. show that the antiretroviral drug AZT restores A3G function in vitroby stimulating expression of a host protein, ASK1, which interferes with the action of Vif.
- Kei Miyakawa
- , Satoko Matsunaga
- & Akihide Ryo
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Article
| Open AccessModelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias
Clinical breast cancers predominantly present luminal features, but experimental models are essentially basal. Here the authors show that luminal cells are significantly less susceptible to viral transduction, and present methods to analyse and overcome the bias in heterogeneous populations.
- William C. Hines
- , Paul Yaswen
- & Mina J. Bissell
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Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology
AbgT family of transporters have previously been implicated in the uptake of folate catabolites but remain poorly understood. Here the authors present a structural and functional characterization of Alcanivorax borkumensisYdaH, an AbgT-type transporter, revealing a unique topology and possible function as a drug efflux pump.
- Jani Reddy Bolla
- , Chih-Chia Su
- & Edward W. Yu
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Article
| Open AccessReconstitution and structure of a bacterial Pnkp1–Rnl–Hen1 RNA repair complex
Bacterial ribotoxins target and cleave RNAs involved in translation, with target organism resistance being mediated by RNA repair systems. Here, Wang et al. identify, report the crystal structure, and characterize the activity of Pnkp1–Rnl–Hen1, a novel RNA repair complex from Capnocytophaga gingivalis.
- Pei Wang
- , Kiruthika Selvadurai
- & Raven H. Huang
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A fungal protease allergen provokes airway hyper-responsiveness in asthma
Airway hyper-responsiveness, a hallmark of asthma, is often associated with sensitization to fungi. Here, the authors show that a fungal protease allergen Asp f13/Alp1 from Aspergillus fumigatuscan promote airway hyper-responsiveness in asthma via its effect on the airway smooth muscle cells.
- Nariman A. Balenga
- , Michael Klichinsky
- & Kirk M. Druey
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Article
| Open AccessAnalysis of immunoglobulin transcripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization
HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.
- Joseph R. Francica
- , Zizhang Sheng
- & Robert A. Seder
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Article
| Open AccessA versatile nano display platform from bacterial spore coat proteins
The densely crosslinked protein coats of bacterial spores are among the most durable static structures in biology. Wu et al.reconstitute the basement layer of a bacterial spore coat on membrane-coated beads, and generate covalently-modified spore-like particles with therapeutic potential.
- I-Lin Wu
- , Kedar Narayan
- & Kumaran S. Ramamurthi
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Article
| Open AccessMammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck
H7N9 bird flu viruses cause mild disease in poultry but can occasionally infect humans with fatal consequences. Here, the authors show that viral genetic diversification is low in ferrets and high in chickens, suggesting that a genetic bottleneck limits H7N9 adaptation to mammals
- Hassan Zaraket
- , Tatiana Baranovich
- & Richard J. Webby
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Article
| Open AccessSystematic functional profiling of transcription factor networks in Cryptococcus neoformans
Cryptococcus neoformans is a fungal pathogen that causes meningoencephalitis. Here the authors describe the production of a gene-deletion mutant collection representing most C. neoformansnon-essential transcription factors, providing insight into the signalling networks that govern the biology and pathogenicity of this fungus.
- Kwang-Woo Jung
- , Dong-Hoon Yang
- & Yong-Sun Bahn
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Article
| Open AccessEighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe
Tuberculosis was once a major killer in Europe. Here the authors use metagenomics to obtain genomic sequences of Mycobacterium tuberculosisfrom human remains from eighteenth-century Hungary, revealing mixed infections within individuals as well as presence of the same strain in two individuals.
- Gemma L. Kay
- , Martin J. Sergeant
- & Mark J. Pallen
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Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome
Dietary fibre is metabolized into short-chain fatty acids by gut bacteria. Here the authors show that these metabolites activate the NLRP3 inflammasome in gut epithelial cells and protect mice from injury-induced colitis, suggesting a mechanism for the benefits of a high-fibre diet.
- Laurence Macia
- , Jian Tan
- & Charles R. Mackay
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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 AccessTriaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate
The emergence of resistant Plasmodiumstrains fuels the search for new antimalarials. Here, the authors present a new class of potent antimalarial compounds, the triaminopyrimidines, that display low toxicity and long half-life in animal models.
- Shahul Hameed P.
- , Suresh Solapure
- & Vasan K. Sambandamurthy
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