Featured
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| Open AccessDynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy
Tuberculosis is a major global health threat. Here, the authors develop a single-cell drug discovery approach and identify a compound that tunes bacterial phenotypic variation. This enhances the activity of anti-tubercular drugs against the pathogen.
- Maxime Mistretta
- , Mena Cimino
- & Giulia Manina
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Article
| Open AccessGut microbiota produces biofilm-associated amyloids with potential for neurodegeneration
The microbiota of the intestinal tract is considered a large biofilm formed by myriads bacteria that have a considerable impact in health and disease. Here, the authors show that biofilm-associated proteins from intestinal microbiota form amyloid-like structures that exacerbate alpha-synuclein pathologies.
- Ariadna Fernández-Calvet
- , Leticia Matilla-Cuenca
- & Jaione Valle
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| Open AccessThe nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression
Here, Murray-Nerger et al use a genome-wide CRISPR/Cas9 screen to show that the nuclear protein SFPQ suppresses lytic reactivation of Epstein-Barr virus by promoting the expression and accumulation of linker histone H1 on the viral genome.
- Laura A. Murray-Nerger
- , Clarisel Lozano
- & Benjamin E. Gewurz
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Article
| Open AccessPhysiological basis for atmospheric methane oxidation and methanotrophic growth on air
Atmospheric methane-oxidizing bacteria constitute the sole biological sink for atmospheric methane. Here, Schmider et al. assess the ability and strategies of seven methanotrophic species to grow with air as sole energy, carbon, and nitrogen source, showing that these bacteria can grow on the trace concentrations of methane, carbon monoxide, and hydrogen present in air.
- Tilman Schmider
- , Anne Grethe Hestnes
- & Alexander T. Tveit
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Article
| Open AccessThe EV71 2A protease occupies the central cleft of SETD3 and disrupts SETD3-actin interaction
Enteroviruses are responsible for several human diseases without treatment. This study describes the molecular interactions between SETD3, actin, and viral 2A in viral replication, providing a framework for the development of host-targeted therapies against enteroviruses.
- Xiaopan Gao
- , Bei Wang
- & Sheng Cui
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Article
| Open AccessMycobacterial biotin synthases require an auxiliary protein to convert dethiobiotin into biotin
Lipid biosynthesis in the pathogen M. tuberculosis depends on biotin for posttranslational modification of key enzymes. Here, Qu et al. identify an auxiliary protein that is required by M. tuberculosis to synthesize biotin.
- Di Qu
- , Peng Ge
- & Dirk Schnappinger
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Article
| Open AccessImportance of social inequalities to contact patterns, vaccine uptake, and epidemic dynamics
Contact patterns influence the spread of infectious diseases, but mathematical models of epidemics typically only account for age differences in contacts. Here, the authors investigate the importance of other sociodemographic characteristics in shaping contact patterns and vaccine uptake using survey data from Hungary.
- Adriana Manna
- , Júlia Koltai
- & Márton Karsai
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Article
| Open AccessSerological evidence of zoonotic filovirus exposure among bushmeat hunters in Guinea
In a serological analysis, Bore et al. utilise serum samples, collected from a cohort of individuals associated with bushmeat hunting and butchering, in the forested region of Guinea, a region close to the epicentre of the 2013–2016 West Africa Ebola virus disease epidemic.
- Joseph Akoi Boré
- , Joseph W. S. Timothy
- & Miles W. Carroll
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Article
| Open AccessADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection
Mice lacking A Disintegrin and Metalloproteinase 9 (ADAM9) do not mount Type 1 interferon responses against encephalomyocarditis infection. Here, Bazzone et al show that ADAM9 regulates innate immune responses via by MDA5.
- Lindsey E. Bazzone
- , Junji Zhu
- & Evelyn A. Kurt-Jones
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Article
| Open AccessSequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity
Here, the authors show that GalNAc-T3 and T7 regulate furin cleavage of the SARS-CoV-2 spike protein via O-glycosylation. This influences viral assembly and infection, highlighting glycosylation as a host defense mechanism.
- Shengjun Wang
- , Wei Ran
- & Yang Mao
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Article
| Open AccessThe vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans
The transition between yeast and hyphae is crucial for the pathogenicity of Candida albicans. Here, Liu et al. show that vacuole fusion is active during hyphal extension and that large vacuoles increase the mechanical forces of hyphae penetrating into organs.
- Yu Liu
- , Ruina Wang
- & Lan Yan
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| Open AccessThe great escape: a Shigella effector unlocks the septin cage
Shigella, an important human pathogen, can secrete effector proteins to invade host cells and evade mechanisms of cell-autonomous immunity. In a new manuscript published in Nature Communications, Xian et al. report that the Shigella kinase effector OspG promotes the ubiquitination of septin cytoskeletal proteins to evade cage entrapment.
- Ana T. López-Jiménez
- , Gizem Özbaykal Güler
- & Serge Mostowy
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Article
| Open AccessMicrobial adaptation to spaceflight is correlated with bacteriophage-encoded functions
Viruses that infect bacteria shape microbial communities. Here, authors show that this may hold for bacteria isolated from the International Space Station, with spacefaring viruses correlated to host adaptation to the spaceflight environment.
- Iris Irby
- & Jared T. Broddrick
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Article
| Open AccessAn antiplasmid system drives antibiotic resistance gene integration in carbapenemase-producing Escherichia coli lineages
It has been predicted that mobilization of resistance genes from plasmid to chromosome is selected by an antibiotic pressure. Here, authors discover an antiplasmid system promoting the chromosomal integration of the carbapenemase gene blaOXA-48.
- Pengdbamba Dieudonné Zongo
- , Nicolas Cabanel
- & Isabelle Rosinski-Chupin
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Article
| Open AccessRisk assessment of a highly pathogenic H5N1 influenza virus from mink
In 2023, a highly pathogenic H5N1 virus caused an outbreak in mink. In the ferret model of influenza, the virus exhibits limited airborne transmissibility and high virulence. These findings indicate heightened pandemic potential of these viruses.
- Katherine H. Restori
- , Kayla M. Septer
- & Troy C. Sutton
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| Open AccessSustained bacterial N2O reduction at acidic pH
Microbial reduction of nitrous oxide to dinitrogen is considered negligible under acidic conditions. However, Guang He et al. show that a co-culture of two bacterial species derived from acidic tropical forest soil can reduce nitrous oxide at pH 4.5.
- Guang He
- , Gao Chen
- & Frank E. Löffler
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Article
| Open AccessOctyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways
The use of oncolytic viruses as a therapy for cancer is limited by mechanisms inhibiting viral replication in the tumor. Here, the authors show that a chemical derivative of itaconate, 4-octyl itaconate, increases oncolytic virus VSVΔ51 efficacy in various cancer models, through decreasing antiviral immunity.
- Naziia Kurmasheva
- , Aida Said
- & David Olagnier
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Article
| Open AccessStructures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation
The authors demonstrate how avian H5N1 influenza A virus polymerase interacts with human ANP32B to facilitate the replication of the viral genetic information in mammalian hosts, revealing insights into cross-species transmission.
- Ecco Staller
- , Loïc Carrique
- & Ervin Fodor
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Article
| Open AccessStructure and genome editing of type I-B CRISPR-Cas
Here the authors present two cryo-EM structures of the Synechocystis sp. PCC 6714 (Syn) type I-B Cascade, revealing the molecular mechanisms that underlie RNA-directed Cascade assembly, target DNA recognition and local conformational changes of the effector complex upon R-loop formation.
- Meiling Lu
- , Chenlin Yu
- & Yibei Xiao
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| Open AccessAnalysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes
Here, Qi et al. assembled ~3000 archaeal genomes from hot springs, capturing temporal dynamics and environmental diversity, and systematically explored functional niches and metabolic handoffs, shedding light on Archaea’s role in biogeochemical cycling.
- Yan-Ling Qi
- , Ya-Ting Chen
- & Zheng-Shuang Hua
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Article
| Open AccessFunctional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning
Deep mutational scanning experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 with different cell lines revealed that mutations at residue 813 of the spike protein reduced TMPRSS2-mediated entry with decreased virulence.
- Ruipeng Lei
- , Enya Qing
- & Lok-Yin Roy Wong
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Article
| Open AccessSevere outcomes of malaria in children under time-varying exposure
Severe pediatric malaria remains a concern in many countries. Here, the authors use an individual-based modeling approach to evaluate the relationship between malaria prevalence and incidence of malaria pediatric hospitalizations, and show how unsteady transmission patterns affect hospitalization rates.
- Pablo M. De Salazar
- , Alice Kamau
- & Melissa A. Penny
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| Open AccessLong-read powered viral metagenomics in the oligotrophic Sargasso Sea
The Sargasso Sea is a natural laboratory for understanding future conditions of warmer oceans and associated nutrient limitation. Here, the authors combined short- and long-read sequencing to survey Sargasso Sea viral communities.
- Joanna Warwick-Dugdale
- , Funing Tian
- & Ben Temperton
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Article
| Open AccessProteome partitioning constraints in long-term laboratory evolution
Adaptive laboratory evolution provides a real-time record of physiological change. In bacteria adapted to glucose over 40 000 generations, this study finds an apparent increase in enzyme efficiency consistent with increased substrate saturation due to loss of a flux sensing mechanism early in adaptation.
- Matteo Mori
- , Vadim Patsalo
- & Matthew Scott
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Article
| Open AccessTargeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy
Efforts to apply targeted protein degradation for antibiotic development are limited by our understanding of prokaryotic protein degradation. Here, the authors establish a chemical-genetic platform and predictive model to determine the degradation potential of essential mycobacterial proteins.
- Harim I. Won
- , Samuel Zinga
- & Junhao Zhu
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Article
| Open AccessSafety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials
In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).
- Nhân Thị Hồ
- , Steven G. Hughes
- & Xuan-Hung Nguyen
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Article
| Open AccessAlpha-glucans from bacterial necromass indicate an intra-population loop within the marine carbon cycle
Phytoplankton blooms provoke bacterioplankton blooms, from which bacterial biomass (necromass) is released via zooplankton grazing and viral lysis. Here, Beidler et al. show that the bacterial biomass, including alpha-glucan polysaccharides generated from the consumption of algal organic matter, is reused by microbes in vitro and during a diatom-dominated bloom.
- Irena Beidler
- , Nicola Steinke
- & Thomas Schweder
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Article
| Open AccessGene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo
The main challenge for anti-HSV therapy is to target latent virus in ganglionic neurons. Here, the authors report a well-tolerated anti-HSV gene editing approach against HSV which targets latent HSV genomes and leads to reductions of ganglionic viral loads, and viral shedding upon reactivation in mouse models.
- Martine Aubert
- , Anoria K. Haick
- & Keith R. Jerome
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Article
| Open AccessTargeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes
Aspergillomarasmine A (AMA) chelates metal ions such as Zn2+ and Ni2+, which are essential for the activity of enzymes that are important for virulence of several pathogens. Here, Sychantha et al. show that AMA inhibits bacterial Ni2+ uptake and Ni-dependent enzymes, and reduces bacterial virulence in an animal infection model.
- David Sychantha
- , Xuefei Chen
- & Gerard D. Wright
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Article
| Open AccessRelationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes
Human leucocyte antigens are important in the adaptive immune response. Here, the authors use data from the UK Biobank linked to electronic health records to investigate the association between genetic variation in HLA alleles and antibody responses to SARS-CoV-2 vaccination and breakthrough COVID-19 outcomes.
- Junqing Xie
- , Beatriz Mothe
- & Daniel Prieto Alhambra
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Article
| Open AccessDetection of Anaplasma and Ehrlichia bacteria in humans, wildlife, and ticks in the Amazon rainforest
In this study, the authors detect diverse Ehrlichia and Anaplasma bacteria in samples from Amazonian wildlife, humans and ticks that are mostly distinct from pathogens detected in the Northern Hemisphere and that might indicate emerging health hazards from tick-borne diseases in the Amazon rainforests.
- Marie Buysse
- , Rachid Koual
- & Olivier Duron
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Article
| Open AccessMolecular basis of bacterial DSR2 anti-phage defense and viral immune evasion
The defense-associated sirtuin 2 (DSR2) system protects bacteria from phages by depleting NAD+. Here, authors elucidate the molecular mechanisms underlying DSR2 assembly, activation, and inhibition, providing important insights into bacterial anti-phage defense.
- Jiafeng Huang
- , Keli Zhu
- & Ang Gao
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Article
| Open AccessThree concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance
Bacterial heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Here, Nicoloff et al. describe how three different mechanisms that increase the copy number of resistance genes can lead to unstable and transient heteroresistance.
- Hervé Nicoloff
- , Karin Hjort
- & Helen Wang
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Article
| Open AccessRapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes
Exponential growth of toxigenic Streptococcus pyogenes M1UK lineage accounted for most of the 2022/2023 invasive infection upsurge in the UK. Authors provide evidence that M1UK first emerged in 2008, has genetic evidence of enhanced fitness, and has disseminated to 3 continents.
- Ana Vieira
- , Yu Wan
- & Shiranee Sriskandan
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Article
| Open AccessMultimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88
Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.
- Simon M. Lauer
- , Maren Reepmeyer
- & Ralf Hoffmann
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| Open AccessAssessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries
High levels of extended spectrum beta-lactamase (ESBL) and carbapenemase encoding genes were detected in bacterial isolates causing neonatal sepsis in LMICs. Authors assess the in vitro activity of three antibiotics (fosfomycin, flomoxef and amikacin) in combination against ESBL-producing Klebsiella pneumoniae and Escherichia coli isolates.
- Biljana Kakaraskoska Boceska
- , Tuba Vilken
- & Herman Goossens
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Article
| Open AccessHerpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase
Encephalitis is a rare and severe complication of Herpes Simplex type 1 infection. Here, Bibert et al describe a genetic variant in a 2-year-old affected child that impairs interferon production in neuronal cells and enhances viral replication.
- Stéphanie Bibert
- , Mathieu Quinodoz
- & Pierre-Yves Bochud
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Article
| Open AccessUnveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi
A-to-I editing in animals is catalyzed by enzymes of the Adenosine Deaminase Acting on RNA family, orthologues of which do not exist in fungi. Here, Feng et al. characterise the enzymes involved in A-to-I mRNA editing in Fusarium graminearum.
- Chanjing Feng
- , Kaiyun Xin
- & Huiquan Liu
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Article
| Open AccessA genetically encoded biosensor to monitor dynamic changes of c-di-GMP with high temporal resolution
The ubiquitous second messenger c-di-GMP regulates many biological processes in bacteria, including cell cycle, motility, virulence and biofilm formation. Here, Kaczmarczyk et al. develop a c-di-GMP biosensor that enables dynamic real-time tracking of c-di-GMP levels in individual living cells.
- Andreas Kaczmarczyk
- , Simon van Vliet
- & Urs Jenal
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Article
| Open AccessThe Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment
Here, Xian et al. use phosphoproteomics to identify that the Shigella effector OspG interacts with a regulator of Cullin-RING ubiquitin ligases to promote the ubiquitination of septins and consequent inhibition of septin cage formation.
- Wei Xian
- , Jiaqi Fu
- & Xiaoyun Liu
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Article
| Open AccessTemporal shifts in 24 notifiable infectious diseases in China before and during the COVID-19 pandemic
Public health and social measures for COVID-19 also impacted the incidence of other infectious diseases. In this study, the authors characterise the impacts of these measures on 24 notifiable infectious diseases in China until December 2023.
- Kangguo Li
- , Jia Rui
- & Tianmu Chen
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Article
| Open AccessBacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer’s disease mouse models
The gut microbiota and microglia play critical roles in Alzheimer’s disease (AD). Here, the authors show that Bacteroides fragilis contributes to AD pathogenesis in mouse models by suppressing immune-mediated microglial clearance of amyloid beta.
- Caroline Wasén
- , Leah C. Beauchamp
- & Howard L. Weiner
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Article
| Open AccessPersistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children
Standard diagnostics are often not able to fully capture submicroscopic parasite dynamics after treatment with antimalarials. In this longitudinal analysis of molecular markers of malaria parasitemia in an Ugandan cohort, authors describe persistence of markers following antimalarial therapy with dynamic and complex multiclonal infections in the initial and post-treatment periods.
- Justin Goodwin
- , Richard Kajubi
- & Sunil Parikh
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Article
| Open AccessAllosteric regulation by c-di-AMP modulates a complete N-acetylglucosamine signaling cascade in Saccharopolyspora erythraea
c-di-AMP is essential for bacterial signaling. Here, the authors identify the GlcNAc-sensing regulator DasR as a c-di-AMP receptor and provide molecular insight into their signaling effect on the developmental and antibiotic biosynthesis control across Actinobacteria.
- Di You
- , Liu-Chang Zhao
- & Bang-Ce Ye
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Article
| Open AccessSeasonal antigenic prediction of influenza A H3N2 using machine learning
This study presents a machine learning model that accurately predicts seasonal antigenic changes of influenza A H3N2 using genetic data. The model’s predictions can aid influenza surveillance, vaccine strain selection, and public health management.
- Syed Awais W. Shah
- , Daniel P. Palomar
- & Matthew R. McKay
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Article
| Open AccessHigh SARS-CoV-2 incidence and asymptomatic fraction during Delta and Omicron BA.1 waves in The Gambia
Many low- and middle-income countries, including The Gambia, had low COVID-19 vaccination coverage during the emergence of the Delta and Omicron variants. Here, the authors perform a prospective household cohort study in the Gambia to investigate the dynamics of SARS-Cov-2 infection in this setting.
- Sheikh Jarju
- , Rhys D. Wenlock
- & Thushan I. de Silva
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Article
| Open AccessReplication competent HIV-guided CRISPR screen identifies antiviral factors including targets of the accessory protein Nef
Innate immune mechanisms are critical for antiviral defense. Here, the authors developed a CRISPR/Cas9-based HIV-driven approach to identify cellular factors compromising viral transcription, assembly, release or infectivity in human T cells. They identify targets of the Nef protein as antiviral factors.
- Caterina Prelli Bozzo
- , Alexandre Laliberté
- & Frank Kirchhoff
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Article
| Open AccessA Toxoplasma gondii O-glycosyltransferase that modulates bradyzoite cyst wall rigidity is distinct from host homologues
A Toxoplasma gondii mucin-type O-glycosyltransferase uses a unique catalytic mechanism to modify bradyzoite cyst wall proteins. A second metal coupled to substrate binding is required for catalysis, while an active site glutamate suggests a double-displacement mechanism.
- Pranav Kumar
- , Tadakimi Tomita
- & Nadine L. Samara
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Article
| Open AccessAn oxylipin signal confers protection against antifungal echinocandins in pathogenic aspergilli
Echinocandins are antifungal drugs that inhibit hyphal growth and induce lysis of hyphal tip compartments in pathogenic Aspergillus species. Here, Calise et al. show that echinocandins induce production of a fungal oxylipin signal, thus triggering hyphal growth changes that reduce hyphal tip lysis and confer echinocandin tolerance.
- Dante G. Calise
- , Sung Chul Park
- & Nancy P. Keller
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