Featured
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Article
| Open AccessThe apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite
Repeating fever is a hallmark of malaria. Here, a large-scale forward genetic screen in malaria-causing Plasmodium falciparum identifies genes associated with parasite tolerance to host fever, including apicoplast targeted isoprenoid biosynthesis—sharing features with artemisinin resistance.
- Min Zhang
- , Chengqi Wang
- & John H. Adams
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Article
| Open AccessTransporter characterisation reveals aminoethylphosphonate mineralisation as a key step in the marine phosphorus redox cycle
Here the authors show that 2-aminoethylphosphonate (2AEP) mineralisation is widespread in the global ocean, operating independently of exogenous inorganic phosphate concentration. They propose 2AEP may be a major route for the regeneration of phosphate required to support marine primary production.
- Andrew R. J. Murphy
- , David J. Scanlan
- & Ian D. E. A. Lidbury
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Article
| Open AccessImpact of tiered restrictions on human activities and the epidemiology of the second wave of COVID-19 in Italy
Italy introduced a system of tiered SARS-CoV-2 control measures in November 2020. Here, the authors quantify the effect of these measures on SARS-CoV-2 transmissibility and hospitalisation, and find reductions across all tiers with the greatest impacts associated with the most restrictive level.
- Mattia Manica
- , Giorgio Guzzetta
- & Stefano Merler
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Article
| Open AccessSingle-cell transcriptome of bronchoalveolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets
A longitudinal analysis of SARS-CoV-2 infection in humans is challenging. Here the authors show a single cell RNA-sequencing analysis of BAL fluid cells from ferrets and characterise the time dependent recruitment of macrophage subsets to the lungs in response to SARS-CoV-2 infection.
- Jeong Seok Lee
- , June-Young Koh
- & Su-Hyung Park
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Article
| Open AccessNeutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants
Here, the authors characterize the neutralization capacity of post-Sputnik V vaccination sera against SARS-CoV-2 variants of concern B.1.1.7 (alpha) and B.1.351 (beta), showing the latter to exhibit resistance to neutralization in vitro.
- Satoshi Ikegame
- , Mohammed N. A. Siddiquey
- & Benhur Lee
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Article
| Open AccessRapid ecosystem-scale consequences of acute deoxygenation on a Caribbean coral reef
How acute deoxygenation events affect tropical marine ecosystems remains poorly understood. This study integrates analyses of coral reef benthic communities with microbial community sequencing to show how a deoxygenation event rapidly altered a shallow tropical coral reef ecosystem in the Caribbean.
- Maggie D. Johnson
- , Jarrod J. Scott
- & Andrew H. Altieri
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Article
| Open AccessSingle-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’
High resolution characterisation of the virus specific T cell response to SARS CoV2 provides further understanding to the immune response to the infection. Here the authors apply a reverse phenotyping approach to interrogate the SARS-CoV-2 T cell compartment at single cell resolution.”
- David S. Fischer
- , Meshal Ansari
- & Kilian Schober
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Article
| Open AccessMechanistic insight into bacterial entrapment by septin cage reconstitution
Septins are cytoskeletal proteins that assemble into complexes and contribute to immunity by entrapping intracellular bacteria in cage-like structures. Here, Lobato-Márquez et al. reconstitute septin cages in vitro using purified recombinant complexes, and study how these recognize bacterial cells and assemble as filaments on their surface.
- Damián Lobato-Márquez
- , Jingwei Xu
- & Serge Mostowy
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Article
| Open AccessIn vivo evolution of an emerging zoonotic bacterial pathogen in an immunocompromised human host
Bordetella hinzii is an emerging pathogen with zoonotic risk to humans, known to be able to cause respiratory tract infection, bacteremia and endocarditis. Here, applying whole genome sequencing to bacterial isolates, the authors characterize the mechanisms driving adaptive evolution in B. hinzii in a patient with interleukin-12 receptor β1 deficiency, suggesting a role for host immune phenotype in shaping within-host pathogen evolution following zoonotic infection.
- A. Launay
- , C.-J. Wu
- & J. P. Dekker
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Article
| Open AccessRational construction of genome-reduced Burkholderiales chassis facilitates efficient heterologous production of natural products from proteobacteria
An efficient chassis for heterologous expression of biosynthetic gene clusters (BGCs) from Gram-negative bacteria is still unavailable. Here, the authors report rational construction of genome-reduced Burkholderials chassis to facilitate production of a class of new compounds by expressing BGC from Chitinimonas koreensis.
- Jiaqi Liu
- , Haibo Zhou
- & Xiaoying Bian
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Article
| Open AccessStrainberry: automated strain separation in low-complexity metagenomes using long reads
Existing long-read de novo assembly methods can partially, but not completely, separate strains. Here, the authors develop Strainberry, a metagenome assembly bioinformatic pipeline that exclusively uses longread data to accurately separate and reconstruct strain genomes from single-sample low-complexity microbiomes.
- Riccardo Vicedomini
- , Christopher Quince
- & Rayan Chikhi
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Article
| Open AccessStructural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics
Macrolides and ketolides antibiotics selectively interfere with the translation of a specific subset of proteins. Here the authors show how the macrolide erythromycin and the ketolide telithromycin interplay with the nascent polypeptide chain to arrest translation.
- Bertrand Beckert
- , Elodie C. Leroy
- & Daniel N. Wilson
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Article
| Open AccessStructure of the molecular bushing of the bacterial flagellar motor
In the basal body of the bacterial flagellum, the LP ring acts as a bushing supporting the distal rod for its rapid and stable rotation. Here, Yamaguchi et al. present the electron cryomicroscopy structure of the LP ring around the rod, shedding light into potential mechanisms involved in stability and assembly of the structure.
- Tomoko Yamaguchi
- , Fumiaki Makino
- & Keiichi Namba
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Article
| Open AccessSmall RNA mediated gradual control of lipopolysaccharide biosynthesis affects antibiotic resistance in Helicobacter pylori
The small RNA RepG modulates expression of chemotaxis receptor TlpB in Helicobacter pylori by targeting a length-variable G-repeat in the tlpB mRNA. Here, Pernitzsch et al. show that RepG also gradually controls lipopolysaccharide biosynthesis, antibiotic susceptibility, and in-vivo colonization of the stomach, by regulating a gene that is co-transcribed with tlpB.
- Sandy R. Pernitzsch
- , Mona Alzheimer
- & Cynthia M. Sharma
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Article
| Open AccessTargeting the latent human cytomegalovirus reservoir for T-cell-mediated killing with virus-specific nanobodies
Human cytomegalovirus (HCMV) can evade immune responses in latent reservoirs, which is a specific problem during transplantation. Here the authors develop a bivalent nanobody that is specific for US28, a viral receptor required by latent HCMV, and show it can partially reactivate the virus and make it susceptible to killing by T cells.
- Timo W. M. De Groof
- , Elizabeth G. Elder
- & Martine J. Smit
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Article
| Open AccessComparative analysis of two paradigm bacteriophytochromes reveals opposite functionalities in two-component signaling
The bacteriophytochrome DrBphP from Deinococcus radiodurans shows high sequence homology to the histidine kinase Agp1 from Agrobacterium fabrum but lacks kinase activity. Here, the authors structurally and biochemically analyse DrBphP and Agp1, showing that DrBphP is a light-activatable phosphatase.
- Elina Multamäki
- , Rahul Nanekar
- & Heikki Takala
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Article
| Open AccessMARCH8 inhibits influenza A virus infection by targeting viral M2 protein for ubiquitination-dependent degradation in lysosomes
The membrane-associated RING-CH (MARCH) proteins are E3 ligases regulating stability of plasma membrane (PM) proteins. Here, Liu et al. show that MARCH8 suppresses Influenza A virus infection in vitro and in vivo through redirecting M2 protein from the PM to lysosomes for degradation.
- Xiaoman Liu
- , Fengwen Xu
- & Fei Guo
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Article
| Open AccessSARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’
Vo’, Italy, is a unique setting for studying SARS-CoV-2 antibody dynamics because mass testing was conducted there early in the pandemic. Here, the authors perform two follow-up serological surveys and estimate seroprevalence, the extent of within-household transmission, and the impact of contact tracing.
- Ilaria Dorigatti
- , Enrico Lavezzo
- & Andrea Crisanti
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Article
| Open AccessThe molecular basis of regulation of bacterial capsule assembly by Wzc
The Wzc–Wza complex forms part of the bacterial extracellular polysaccharides synthesis machinery, where cycling of the Wzc between phosphorylation states is crucial to both synthesis and export. Here the authors report the structure of the Wzc octamer and provide insight into its regulation through phosphorylation.
- Yun Yang
- , Jiwei Liu
- & James H. Naismith
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Article
| Open AccessRenewable fatty acid ester production in Clostridium
Esters can be used as fuels and specialty chemicals for food flavoring, cosmetic and pharmaceutical industries. Here, the authors systematically engineer clostridia, including discovery and deletion of prophages to increase strain stability, for the production of butyl acetate and butyl butyrate from corn stover at low cost.
- Jun Feng
- , Jie Zhang
- & Yi Wang
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Article
| Open AccessSARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance
SARS-CoV-2 infection damages the airways. Here the authors show that SARS-CoV-2 infection induces the rapid loss of airway motile cilia, resulting in altered cilia clearance function. Cilia loss is preceded by reduced expression of the ciliogenesis regulator Foxj1.
- Rémy Robinot
- , Mathieu Hubert
- & Lisa A. Chakrabarti
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Article
| Open AccessOil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2
Bottlenecks in qPCR-based COVID-19 diagnostics include the lengthy multistep process and reagent shortages. Here the authors report OIL-TAS which integrates RNA extraction and detection into a single device.
- Duane S. Juang
- , Terry D. Juang
- & David J. Beebe
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Article
| Open AccessBroadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses
Noroviruses can cause gastroenteritis and there is currently no licensed vaccine or specific treatment available. Here, the authors isolate human monoclonal antibodies and characterize one antibody (NORO-320) with broad reactivity to genogroup I and II noroviruses.
- Gabriela Alvarado
- , Wilhelm Salmen
- & James E. Crowe Jr.
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Article
| Open AccessIntracellular lipid droplet accumulation occurs early following viral infection and is required for an efficient interferon response
Lipid droplets (LDs) are recognized as dynamic organelles and scaffolding platforms to regulate signalling cascades. Here, Monson et al. provide evidence that LDs are involved in regulation of an early antiviral immune response specifically through the enhanced modulation of IFN following viral infection in vitro and in vivo.
- E. A. Monson
- , K. M. Crosse
- & K. J. Helbig
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Article
| Open AccessGeminiviruses encode additional small proteins with specific subcellular localizations and virulence function
Geminiviruses are small plant-infecting viruses. Here the authors screen the geminivirus genome for small open reading frames that may have been previously overlooked and show that one encodes a protein named V3 that localizes to the Golgi and acts as an RNA silencing suppressor.
- Pan Gong
- , Huang Tan
- & Xueping Zhou
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Article
| Open AccessReprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance
Cas13b can be harnessed to target and degrade RNA transcripts inside a cellular environment. Here the authors reprogram Cas13b to target SARSCoV-2 transcripts in infected mammalian cells and reveal its resilience to variants thanks to single mismatch tolerance.
- Mohamed Fareh
- , Wei Zhao
- & Joseph A. Trapani
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Article
| Open AccessEnergy efficiency and biological interactions define the core microbiome of deep oligotrophic groundwater
Ecological constraints on microbial niches in oligotrophic deep groundwaters remain elusive. This study provides support for the existence of a common core microbiome in two deep groundwater biomes of the Fennoscandian Shield using a genome-resolved, integrated omics analysis.
- Maliheh Mehrshad
- , Margarita Lopez-Fernandez
- & Mark Dopson
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Article
| Open AccessStructural basis of the membrane intramolecular transacylase reaction responsible for lyso-form lipoprotein synthesis
In Gram-positive bacteria, lipoprotein intramolecular transacylase Lit produces a lipoprotein variant with less immunogenicity. As such, Lit can be viewed as a virulence factor. Here, structural and functional characterization of the enzyme provides insight into its catalytic mechanism, setting the stage for future studies of Lit as a target for new antibiotics.
- Samir Olatunji
- , Katherine Bowen
- & Martin Caffrey
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Article
| Open AccessNative flagellar MS ring is formed by 34 subunits with 23-fold and 11-fold subsymmetries
The bacterial flagellar MS ring is a core transmembrane complex within the flagellar basal body. Here, cryoEM analysis suggests that the MS ring is formed by 34 full-length FliF subunits, with 23- and 11-fold subsymmetries in the inner and middle M ring, respectively.
- Akihiro Kawamoto
- , Tomoko Miyata
- & Keiichi Namba
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Matters Arising
| Open AccessRe-evaluating the evidence for a universal genetic boundary among microbial species
- Connor S. Murray
- , Yingnan Gao
- & Martin Wu
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Article
| Open AccessMapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies
Emerging SARS-CoV-2 mutants may escape neutralization by antibodies. Here, the authors use deep mutational scanning to identify mutations in the RBD that escape human monoclonal antibodies or convalescent plasmas.
- Allison J. Greaney
- , Tyler N. Starr
- & Jesse D. Bloom
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Article
| Open AccessNUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
Nucleoside analogs (NNA), such as acyclovir (ACV) and ganciclovir (GCV), are widely used as anti-virals to treat herpes virus infection. Here, Nishii et al. show that diphosphatase NUDT15 hydrolyzes ACV and GCV, therewith reducing NNA activity in vitro and link NUDT15 variation to inter-patient variability in ACV and GCV therapeutic effects.
- Rina Nishii
- , Takanori Mizuno
- & Jun J. Yang
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Article
| Open AccessA genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex
Klebsiella pneumoniae is a pathogen of increasing public health concern and antimicrobial resistance is becoming more prevalent. Here, the authors describe a K. pneumoniae genotyping tool, Kleborate, that can be used to identify lineages and detect antimicrobial resistance and virulence loci.
- Margaret M. C. Lam
- , Ryan R. Wick
- & Kathryn E. Holt
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Article
| Open AccessTranslocation of vaginal microbiota is involved in impairment and protection of uterine health
Here, the authors present a comparative analyses on vaginal and uterine microbiota in 1223 samples derived from 655 women with chronic endometritis, which, combined with animal experiments, characterize the microbial translocation in the female reproductive tract and its role in modulating uterine health.
- Jinfeng Wang
- , Zhanzhan Li
- & Fangqing Zhao
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Article
| Open AccessThe role of membrane destabilisation and protein dynamics in BAM catalysed OMP folding
The folding of outer membrane proteins (OMPs) is catalyzed by the βbarrel assembly machinery (BAM). Here, structural and functional analyses of BAM stabilized in distinct conformations elucidate the roles of lateral gate opening and interactions of BAM with the lipid bilayer in OMP assembly.
- Paul White
- , Samuel F. Haysom
- & Sheena E. Radford
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Matters Arising
| Open AccessReply to: “Re-evaluating the evidence for a universal genetic boundary among microbial species”
- Luis M. Rodriguez-R
- , Chirag Jain
- & Konstantinos T. Konstantinidis
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Article
| Open AccessAsymmetric reconstruction of mammalian reovirus reveals interactions among RNA, transcriptional factor µ2 and capsid proteins
Mammalian reovirus (MRV) is a double-stranded RNA (dsRNA) virus that affects the gastrointestinal and respiratory tracts. Here, the authors present the 3.3 Å cryo-EM asymmetric reconstruction of transcribing MRV that reveals the organization of the dsRNA genome, RNA interaction with the polymerase complex, and how the polymerase interacts extensively with its co-factor, µ2, to form a transcription enzyme complex, which engages and regulates RNA transcription.
- Muchen Pan
- , Ana L. Alvarez-Cabrera
- & Z. Hong Zhou
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Article
| Open AccessThe molecular basis for SARS-CoV-2 binding to dog ACE2
Many domestic animals, among them dogs, have been infected with SARS-CoV-2 during the COVID-19 pandemic. Here, the authors present the crystal structure of the SARS-CoV-2 spike protein receptor binding domain (RBD) bound to its receptor, dog angiotensin-converting enzyme 2 (dACE2), and show that the RBD N501Y mutation increases the infectivity and host range of SARS-CoV-2, which highlights the need to monitor emerging SARS-CoV-2 mutations in domestic animals.
- Zengyuan Zhang
- , Yanfang Zhang
- & Yeping Sun
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Article
| Open AccessGlobal distribution patterns of marine nitrogen-fixers by imaging and molecular methods
Nitrogen fixation by diazotrophs is critical for marine primary production. Using Tara Oceans datasets, this study combines a quantitative image analysis pipeline with metagenomic mining to provide an improved global overview of diazotroph abundance, diversity and distribution.
- Juan José Pierella Karlusich
- , Eric Pelletier
- & Rachel A. Foster
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Article
| Open AccessSuppressing peatland methane production by electron snorkeling through pyrogenic carbon in controlled laboratory incubations
Warmer and drier conditions are increasing the frequency of forest fires, which in turn produce pyrogenic carbon. Here the authors show that accumulation of pyrogenic carbon can suppress post-fire methane production in northern peatlands and can effectively buffer fire-derived greenhouse gas emissions.
- Tianran Sun
- , Juan J. L. Guzman
- & Largus T. Angenent
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Article
| Open AccessMonocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity
The host immune response plays a critical role in the immunopathology of SARS-CoV2. Here the authors combine a systems biology approach to implicate monocytes as key drivers of cytokine storm and disturbed neutrophil activation in COVID-19 disease severity.
- L. Vanderbeke
- , P. Van Mol
- & J. Wauters
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Article
| Open AccessStructural basis for recognition and regulation of arenavirus polymerase L by Z protein
Junin virus (JUNV) causes Argentine hemorrhagic fever and encodes the large protein (L) of the RNA dependent RNA polymerase (RdRp) and its regulator, the matrix zinc-binding protein (Z). Here, the authors present the 3.54 Å cryo-EM structure of the complex of JUNV L with Z, and they propose a model of how JUNV L is regulated by Z during the viral life cycle and RNA synthesis.
- Huiling Kang
- , Jingyuan Cong
- & Zihe Rao
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Article
| Open AccessQuantifying nitrogen fixation by heterotrophic bacteria in sinking marine particles
N2 fixation by heterotrophic bacteria has recently been found to take place on sinking marine particles, but an understanding of its regulation and importance is lacking. Here the authors develop a trait-based model for this N2 fixation, finding that this once overlooked process could have global importance.
- Subhendu Chakraborty
- , Ken H. Andersen
- & Lasse Riemann
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Article
| Open AccessXyloglucan processing machinery in Xanthomonas pathogens and its role in the transcriptional activation of virulence factors
Xyloglucans are polysaccharides found in plant cell walls. Here, the authors describe the xyloglucan depolymerization machinery of phytopathogenic Xanthomonas bacteria, and show that sugars released by this system induce the expression of key virulence factors driving pathogenesis.
- Plinio S. Vieira
- , Isabela M. Bonfim
- & Mario T. Murakami
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Article
| Open AccessCVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2
Emerging SARS-CoV-2 variants with mutations in the spike protein raise concerns regarding vaccine efficacy. Here, the authors show that two spike encoding mRNA vaccines in preclinical and clinical development protect human ACE2 mice from the B.1.351 variant of concern and ancestral B BavPat1.
- Donata Hoffmann
- , Björn Corleis
- & Martin Beer
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Article
| Open AccessAn epidemic Zika virus isolate suppresses antiviral immunity by disrupting antigen presentation pathways
The CD8 T cell response to Zika virus is known to be a critical component of the host immune response to infection. Here the authors show a Zika virus isolate specific disruption of antigen processing that impacts the host response and impairs viral clearance providing evidence of isolate specific impacts on the immune response to infection
- Ryan D. Pardy
- , Stefanie F. Valbon
- & Martin J. Richer
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Article
| Open AccessThe bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis
Phospholipase ExoU from Pseudomonas aeruginosa acts on plasma membrane lipids in infected cells, causing membrane rupture and host cell necrosis. Here, Deruelle et al. show that once injected into the host cytoplasm, ExoU requires a host chaperone found on secretory vesicles to reach the plasma membrane and exerts its phospholipase activity.
- Vincent Deruelle
- , Stéphanie Bouillot
- & Philippe Huber
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Article
| Open AccessNon-invasive plasma glycomic and metabolic biomarkers of post-treatment control of HIV
Current HIV cure-focused clinical trials rely on analytic treatment interruption (ATI) to evaluate post-treatment control (PTC). Here, combining untargetted metabolomics and glycomics in two HIV clinical cohorts, in vitro assays, and machine learning, the authors identify and validate metabolic and glycomic biomarkers linked to inflammatory pathways and HIV latency reactivation associated with PTC, suggesting non-invasive biomarkers as an alternative to predict HIV remission.
- Leila B. Giron
- , Clovis S. Palmer
- & Mohamed Abdel-Mohsen
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Article
| Open AccessPangenomics reveals alternative environmental lifestyles among chlamydiae
Chlamydiae are strictly intracellular bacteria that exist in a wide variety of environments but the diversity of the phylum is not well described. Here, the authors analyze 82 metagenome-assembled genomes, identify seven new families, and describe genomic signals of metabolic diversity.
- Stephan Köstlbacher
- , Astrid Collingro
- & Matthias Horn
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