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| Open AccessSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
SARS-CoV-2 infection can lead to progressive pathology in patients with COVID-19, but information for this disease progression is sparse. Here the authors use multi-omics approach to profile the immune responses of patients, assessing immune repertoire and effects of tocilizumab treatments, to find a dyssynchrony between innate and adaptive immunity in progressive COVID-19.
- Avraham Unterman
- , Tomokazu S. Sumida
- & Charles S. Dela Cruz
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Article
| Open AccessShared features and reciprocal complementation of the Chlamydomonas and Arabidopsis microbiota
Plants and algae associate with microbial communities that affect their growth and development. Here, the authors characterize the microbiota associated with a unicellular alga in soil, revealing extensive taxonomic and functional overlap with the root microbiota of land plants.
- Paloma Durán
- , José Flores-Uribe
- & Ruben Garrido-Oter
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Article
| Open AccessMultimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong
Adverse events resulting from COVID-19 vaccination are a public health concern and it is not known whether pre-existing conditions may impose an increased risk. Here, using electronic health records from Hong Kong, the authors show that adverse events are rare for all groups, and there is no evidence of risk modification due to multimorbidity.
- Francisco Tsz Tsun Lai
- , Lei Huang
- & Ian Chi Kei Wong
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Article
| Open AccessResolving the conflict between antibiotic production and rapid growth by recognition of peptidoglycan of susceptible competitors
Microbial communities employ a variety of strategies to compete against competitors sharing their niche, for instance, by producing antibiotics. This study reveals that antibiotics produced by Bacillus subtilis act synergistically to eliminate phylogenetically distinct competitors and are regulated accordingly.
- Harsh Maan
- , Maxim Itkin
- & Ilana Kolodkin-Gal
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Article
| Open AccessCirculating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2
El-Shennawy et al. report that ACE2+ circulating extracellular vesicles (evACE2) are associated with COVID-19 severity and that evACE2 inhibits the infection of SARS-CoV-2 variants of concern at a higher efficacy than soluble ACE2.
- Lamiaa El-Shennawy
- , Andrew D. Hoffmann
- & Huiping Liu
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Article
| Open AccessStructure of a type IV secretion system core complex encoded by multi-drug resistance F plasmids
Bacteria conjugatively transfer DNA through type IV secretion systems (T4SSs). Here, the authors report the structure of a T4SS outer-membrane core complex (OMCC), revealing how a distinct C13:C17 symmetry mismatch exhibited by peripheral ring and central cone substructures is accommodated.
- Xiangan Liu
- , Pratick Khara
- & Bo Hu
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Article
| Open AccessCombination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae
In this case study of a patient with fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term antibiotic therapy, the authors use a combination therapy of pre-adapted bacteriophage and antibiotics resulting in clinical, microbiological and radiological improvement.
- Anaïs Eskenazi
- , Cédric Lood
- & Jean-Paul Pirnay
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Article
| Open AccessResolving the structure of phage–bacteria interactions in the context of natural diversity
Understanding the interactions between bacteria and their viruses (phages) in natural communities is a major challenge. Here, the authors isolate and study large numbers of marine Vibrio bacteria and their phages, and find that lytic interactions are sparse and many phages are host-strain-specific, but nevertheless recombination between some phages is common.
- Kathryn M. Kauffman
- , William K. Chang
- & Libusha Kelly
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Article
| Open AccessA polytherapy based approach to combat antimicrobial resistance using cubosomes
An increasing prevalence of Gram-negative bacteria increases the interest in nanotherapies to treat antibiotic resistance. Here, the authors examine the antimicrobial activity of polymyxin-loaded cubosomes and explore a polytherapy treatment of pathogens with cubosomes in combination with polymyxin.
- Xiangfeng Lai
- , Mei-Ling Han
- & Hsin-Hui Shen
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Article
| Open AccessThe three-dimensional structure of Epstein-Barr virus genome varies by latency type and is regulated by PARP1 enzymatic activity
Genome folding in the nucleus plays an important role in regulating gene expression. Here the authors show that 3D genome architecture also plays an important role for gene expression adaptability for the Epstein-Barr Virus (EBV), a virus that is associated with cancer. They also observe major changes in the fold of the EBV chromosome between silent and transcriptional active viral genomes.
- Sarah M. Morgan
- , Hideki Tanizawa
- & Italo Tempera
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Article
| Open AccessDistinct kinetics of antibodies to 111 Plasmodium falciparum proteins identifies markers of recent malaria exposure
Serological markers of recent Plasmodium falciparum infection could be useful to estimate incidence. Here, the authors identify a combination of five serological markers to detect exposure to infection within the previous three months with >80% sensitivity and specificity.
- Victor Yman
- , James Tuju
- & Anna Färnert
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Article
| Open AccessPantothenate biosynthesis is critical for chronic infection by the neurotropic parasite Toxoplasma gondii
Coenzyme A (CoA) is an essential metabolite found in all organisms and its synthesis involves five conserved enzymatic steps and uses pantothenate (Pan) as a precursor. Here, Lunghi et al. examine the Pan synthesis pathway in Toxoplasma gondii and find that Pan is crucial for the establishment of chronic but not acute infection.
- Matteo Lunghi
- , Joachim Kloehn
- & Dominique Soldati-Favre
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Article
| Open AccessMicrobiome differential abundance methods produce different results across 38 datasets
Many microbiome differential abundance methods are available, but it lacks systematic comparison among them. Here, the authors compare the performance of 14 differential abundance testing methods on 38 16S rRNA gene datasets with two sample groups, and show ALDEx2 and ANCOM-II produce the most consistent results.
- Jacob T. Nearing
- , Gavin M. Douglas
- & Morgan G. I. Langille
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Article
| Open AccessModel-based evaluation of alternative reactive class closure strategies against COVID-19
Reactive school class closures have been widely implemented to mitigate COVID-19 outbreaks. Here, the authors show that, compared to symptom-prompted PCR testing, screening for cases in schools with antigen tests leads to greater reductions in infection rates in both students and the wider community.
- Quan-Hui Liu
- , Juanjuan Zhang
- & Marco Ajelli
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Article
| Open AccessGenetic diversity in terrestrial subsurface ecosystems impacted by geological degassing
Geological degassing can impact subsurface metabolism. Here, the authors describe microbial communities from a cold-water geyser are described and compared with other deep subsurface sites, finding a key role for an uncultivated archaeon.
- Till L. V. Bornemann
- , Panagiotis S. Adam
- & Alexander J. Probst
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Article
| Open AccessStructural basis of prokaryotic ubiquitin-like protein engagement and translocation by the mycobacterial Mpa-proteasome complex
Pup is the bacterial analog of ubiquitin for targeting proteins to the proteasome. Here, the authors use cryoEM to visualize structures of the Mycobacterium tuberculosis proteasome translocating a Pup-tagged substrate.
- Mikhail Kavalchuk
- , Ahmad Jomaa
- & Eilika Weber-Ban
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Article
| Open AccessGut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion
Metabolic conditions associated with alterations of the gut microbiome, such as obesity and diabetes, predispose to gallstone disease. Here the authors demonstrate that the gut microbiome, in particular the genus Desulfovibrionale, contribute to gallstone formation in mice.
- Hai Hu
- , Wentao Shao
- & Aihua Gu
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Article
| Open AccessMapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies
Influenza viruses carry their own RNAdependent RNA-polymerase that is highly conserved and a promising anti-viral target. Combining functional and structural data, Keown et al. characterise the inhibitory effect of nanobodies on 1918 pandemic H1N1 influenza strain polymerase complex and identify sensitive sites interfering with polymerase activity in vitro.
- Jeremy R. Keown
- , Zihan Zhu
- & Jonathan M. Grimes
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Article
| Open AccessmolBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history
Here, Burk et al. develop an algorithm to diagnose bacterial vaginosis (BV) using the 16S rRNA gene, called molBV, which they use to profile the inflammatory landscape of BV and predict progression of human papillomavirus infection to cervical pre-cancer.
- Mykhaylo Usyk
- , Nicolas F. Schlecht
- & Robert D. Burk
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Article
| Open AccessNeutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding
Pseudomonas aeruginosa employs lectins to bind to its host cells, and is known to be the major cause of lung infections. Lectin B (LecB) from Pseudomonas aeruginosa binds specifically to galactose and fucose and is important for pathogenicity, adhesion and biofilm formation. In this work, the neutron crystal structure (1.9 Å) of the deuterated LecB/Ca/fucose complex is reported. The structure, in combination with perdeuteration of the ligand and the receptor allowed the observation of hydrogen atoms, protonation states and hydrogen bonds involved in the interaction between pathogenic bacteria and host cells. Thus the study provides structural insights into the mechanism of high affinity binding of LecB to its targets.
- Lukas Gajdos
- , Matthew P. Blakeley
- & Anne Imberty
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Article
| Open AccessAge-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets
Here, Kim et al. characterize SARS-CoV-2 infection in juvenile, young, and old aged ferrets to provide a further understanding of differences in COVID-19 severity in humans at different ages. Aged ferrets have higher viral loads, shed virus longer, and mimic the transcriptomic profile of severely infected patients.
- Young-Il Kim
- , Kwang-Min Yu
- & Young Ki Choi
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Article
| Open AccessPyridylpiperazine-based allosteric inhibitors of RND-type multidrug efflux pumps
Efflux transporters of the RND family confer resistance to multiple antibiotics in Gram-negative bacteria. Here, the authors identify pyridylpiperazine-based compounds that potentiate antibiotic activity in E. coli through allosteric inhibition of its primary RND transporter.
- Coline Plé
- , Heng-Keat Tam
- & Ruben C. Hartkoorn
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Article
| Open AccessAn assembly of nuclear bodies associates with the active VSG expression site in African trypanosomes
A Variant Surface Glycoprotein (VSG) coat protects bloodstream form T. brucei. Applying super-resolution microscopy Budzak et al. characterize a set of nuclear bodies, which associate with the active expression site in bloodstream form T. brucei and highlight the importance of trans-splicing for transcription of VSG.
- James Budzak
- , Robert Jones
- & Gloria Rudenko
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Article
| Open AccessGain-of-function genetic screening identifies the antiviral function of TMEM120A via STING activation
Understanding the interplay between host and viral factors during infection is essential for the interactome of infection. Here the authors perform a gain-of-function screen to identify factors involved during Zika virus infection and identify TMEM120A as a key factor in the STING mediated immune responses.
- Shuo Li
- , Nianchao Qian
- & Xu Tan
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Article
| Open AccessHyphal compartmentalization and sporulation in Streptomyces require the conserved cell division protein SepX
Streptomyces bacteria undergo two modes of cell division: formation of cross-walls in hyphae, leading to multicellular compartments, and septation for release of unicellular spores. Here, Bush et al. identify a protein that is important for both cell division modes in Streptomyces, likely by contributing to stabilization of the divisome.
- Matthew J. Bush
- , Kelley A. Gallagher
- & Susan Schlimpert
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Article
| Open AccessTASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV
The human silencing hub (HUSH) complex, which includes TASOR, deposits repressive marks on HIV proviruses, resulting in gene repression. Here, Matkovic et al. show that TASOR interacts with RNA Polymerase II, predominantly under its elongating state, and RNA degradation proteins to repress HIV provirus expression.
- Roy Matkovic
- , Marina Morel
- & Florence Margottin-Goguet
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Article
| Open AccessCross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts
While cross-reactive immunity between human coronavirus and SARS-CoV-2 may contribute to host protection, validating evidences are still scarce. Here the authors assess a cohort of 52 donors with immediate-early contact with SARS-CoV-2 to correlate higher frequency of cross-reactive T cells with lower infection rate.
- Rhia Kundu
- , Janakan Sam Narean
- & Ajit Lalvani
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Article
| Open AccessA bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo
Here, the authors isolate and characterize a bispecific monomeric nanobody that induces dimerization of SARS-CoV-2 spike trimers, neutralizes variants of concerns as well as SARS-CoV, and inhibits SARS-CoV-2 infection in mice.
- Leo Hanke
- , Hrishikesh Das
- & Gerald M. McInerney
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Article
| Open AccessPhylogenetically and functionally diverse microorganisms reside under the Ross Ice Shelf
The Ross Ice Shelf is the most extensive ice shelf of Antarctica and isolates the underlying ocean from sunlight. Here the authors use multi-omics to unravel the phylogenetic and functional diversity of microbial life in this ecosystem.
- Clara Martínez-Pérez
- , Chris Greening
- & Federico Baltar
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Article
| Open AccessCrystal structure and functional implication of bacterial STING
The bacterial Cyclic-oligonucleotide-Based Anti-phage Signaling System (CBASS) contains a CD-NTase that synthesizes cyclic di- and tri-nucleotides, and bacterial STING proteins recognize c-di-GMP generated by CD-NTase during phage infection and signal the infected bacteria to commit suicide. Here, the authors provide insights into the molecular basis for c-di-GMP recognition of bacterial STING proteins by determining two STING protein crystal structures with bound c-di-GMP from Prevotella corporis and Myroides sp. ZB35.
- Tzu-Ping Ko
- , Yu-Chuan Wang
- & Yeh Chen
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Article
| Open AccessDynamics of spike-and nucleocapsid specific immunity during long-term follow-up and vaccination of SARS-CoV-2 convalescents
Waning immunity to SARS-CoV-2 is of concern. Here the authors follow spike- and nucleocapsid specific immunity in convalescent individuals for 9 months observing a decline in antibody levels but persisting T cell response. Vaccination approximately 11 months after infection boosts antibody and T cell immunity.
- Nina Koerber
- , Alina Priller
- & Percy A. Knolle
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Article
| Open AccessLatency reversal plus natural killer cells diminish HIV reservoir in vivo
Here, Kim et al. describe a new kick and kill strategy utilizing a single administration of a protein kinase C modulator and latency reversing agent in combination with injections of allogeneic peripheral blood natural killer cells diminishes the HIV reservoir in HIV-infected humanized mice.
- Jocelyn T. Kim
- , Tian-Hao Zhang
- & Jerome A. Zack
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Article
| Open AccessStructural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors
Structural immunology is critical in understanding the interplay between the immune response and the infective agent but such studies in T cells and SARS-CoV-2 lag behind those of antibodies and B-cell receptors. Here the authors assess recognition of SARS-CoV-2 spike epitopes and their natural variants by public and private T cell receptors.
- Daichao Wu
- , Alexander Kolesnikov
- & Roy A. Mariuzza
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Article
| Open AccessConformational dynamics of the Beta and Kappa SARS-CoV-2 spike proteins and their complexes with ACE2 receptor revealed by cryo-EM
Here, the authors provide insights into the conformational dynamics of the Beta and Kappa SARS-CoV-2 spike (S) proteins by determining their cryo-EM structures, which revealed a distribution shift towards the open state for both variants compared to the wild-type S protein. They also present the structures of the Kappa and Beta S-ACE2 complexes, where a population shift towards the three receptor-binding domain up conformation was observed. In combination with biochemical data these structures show how the S protein variants efficiently recognize and bind to ACE2.
- Yifan Wang
- , Cong Xu
- & Yao Cong
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Article
| Open AccessSingle dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
Here the authors generate a live-attenuated Zika vaccine based on a clinically proven dengue virus serotype-2 vaccine backbone and show that one dose protects mice and non-human primates from Zika virus infection.
- Whitney R. Baldwin
- , Holli A. Giebler
- & Claire Y.-H. Huang
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Article
| Open AccessThe long non-coding RNA landscape of Candida yeast pathogens
Long non-coding RNAs (lncRNAs) play roles in key cellular processes, but remain largely unexplored in fungal pathogens such as Candida. Here, Hovhannisyan and Gabaldón analyze thousands of sequencing datasets to infer and characterize the lncRNA repertoires of five Candida species, paving the way for their future functional characterization.
- Hrant Hovhannisyan
- & Toni Gabaldón
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Article
| Open AccessKaposi’s sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda
The T cell response to Kaposi sarcoma-associated herpesvirus is critical to controlling infection and immunopathology but has been poorly explored in immunocompetent patients. Here the authors characterise the T cell response to the Kaposi sarcoma-associated herpesvirus proteome in immunocompetent patients from rural Uganda.
- Angela Nalwoga
- , Romin Roshan
- & Denise Whitby
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Article
| Open AccessCritical Assessment of MetaProteome Investigation (CAMPI): a multi-laboratory comparison of established workflows
The authors present CAMPI, a large-scale multi-lab comparison of diverse metaproteomics workflows. CAMPI provides insights into the robustness of current methods, suggests further improvements to the field, and may pave the way for future community-driven metaproteomics projects.
- Tim Van Den Bossche
- , Benoit J. Kunath
- & Thilo Muth
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Article
| Open AccessImpact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants
Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.
- Edward P. K. Parker
- , Christina Bronowski
- & Miren Iturriza-Gómara
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Article
| Open AccessGenomic signatures of pre-resistance in Mycobacterium tuberculosis
Signals of antimicrobial resistance in pathogen genomes may be detectable before the organism evolves an antimicrobial resistance phenotype. Here, the authors investigate this hypothesis using Mycobacterium tuberculosis data from Peru and identify candidate “pre-resistance” markers.
- Arturo Torres Ortiz
- , Jorge Coronel
- & Louis Grandjean
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Article
| Open AccessA randomized study to evaluate safety and immunogenicity of the BNT162b2 COVID-19 vaccine in healthy Japanese adults
Here the authors provide the interim analysis of an ongoing phase 1/2 study of the BNT162b2 vaccine in healthy Japanese adults. They report mainly mild to moderate local reactions and no serious adverse events as well as good antibody induction one month after the second dose.
- Miwa Haranaka
- , James Baber
- & Stephen Lockhart
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Article
| Open AccessConvergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation
Double membrane vesicles (DMV) are used as replication organelles by several RNA viruses. Applying proteomics and lipidomics, Tabata and Prasad et al. find that two cellular acyltransferases (AGPAT1/2), responsible for synthesis of phosphatidic acid, play a role in the DMV-biogenesis of HCV and SARS-CoV-2, highlighting a common biogenesis mechanism for evolutionary distant positive-strand RNA viruses.
- Keisuke Tabata
- , Vibhu Prasad
- & Ralf Bartenschlager
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Article
| Open AccessEstimating the strength of selection for new SARS-CoV-2 variants
Identifying new SARS-CoV-2 genetic variants of concern is important to inform public health strategies, but distinguishing those causing a significant threat is challenging. Here, the authors develop and evaluate two models for assessing the strength of selection for new variants.
- Christiaan H. van Dorp
- , Emma E. Goldberg
- & Ethan O. Romero-Severson
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Article
| Open AccessIncreased transmissibility of SARS-CoV-2 lineage B.1.1.7 by age and viral load
Establishing the relative transmissibility of emerging variants of SARS-CoV-2 is key for pandemic management. Here, the authors use full-population administrative data from Denmark linked to PCR test results and estimate that the Alpha variant was ~60% higher than other strains circulating in early 2021.
- Frederik Plesner Lyngse
- , Kåre Mølbak
- & Carsten Thure Kirkeby
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Article
| Open AccessForward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains
Some isolates of the emerging fungal pathogen Candida auris can form cellular aggregates or filaments. Here, Santana and O’Meara use Agrobacterium-mediated transformation and a CRISPR-Cas9 system to identify several genes that regulate C. auris morphogenesis.
- Darian J. Santana
- & Teresa R. O’Meara
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Article
| Open AccessSerological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England
The UK extended the interval until the second COVID-19 vaccine dose up to 12 weeks. Here, the authors show in a cohort of 750 participants aged 50–89 years that the extended schedule results in higher antibody titers and estimate a higher vaccine effectiveness for the extended schedule.
- Gayatri Amirthalingam
- , Jamie Lopez Bernal
- & Mary E. Ramsay
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Article
| Open AccessGenetic determinants of endophytism in the Arabidopsis root mycobiome
Plant roots host diverse fungal communities that affect plant health. Here, Mesny et al. use comparative genomics and transcriptomics of fungal isolates from the Arabidopsis thaliana root mycobiota, together with root colonization assays, to identify genetic determinants of endophytism.
- Fantin Mesny
- , Shingo Miyauchi
- & Stéphane Hacquard
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Article
| Open AccessMolecular basis of enzymatic nitrogen-nitrogen formation by a family of zinc-binding cupin enzymes
Enzymes involved in the synthesis of nitrogen-nitrogen bond containing molecules have been identified but the processes remain largely unknown. Here, the authors use biochemical characterisation and computer modelling to study the molecular basis of hydrazine bond formation by a family of di-domain enzymes.
- Guiyun Zhao
- , Wei Peng
- & Yi-Ling Du
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Article
| Open AccessPopulation analysis of Legionella pneumophila reveals a basis for resistance to complement-mediated killing
The bacterium Legionella pneumophila can cause severe respiratory infection, but is typically a symbiont of free-living amoeba. Here, the authors analyse the genomes of 902 clinical and environmental isolates, and identify a bacterial gene that is strongly associated with human infection and confers resistance to complement-mediated killing.
- Bryan A. Wee
- , Joana Alves
- & J. Ross Fitzgerald
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