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Article
| Open AccessVirus diversity, wildlife-domestic animal circulation and potential zoonotic viruses of small mammals, pangolins and zoo animals
Monitoring the diversity of viruses infecting animals is important for assessing zoonotic risk. Here, the authors use metatranscriptomics to characterise the viromes of small mammals, pangolins, and zoo animals in China to identify potentially zoonotic viruses.
- Xinyuan Cui
- , Kewei Fan
- & Yongyi Shen
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Article
| Open AccessA host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi
Current treatment of fungal infections is threatened by emerging antifungal drug resistance. In this work, the authors explore the synergistic activity of a host defense peptide mimetic, brilacidin, with caspofungin against a panel of fungal strains.
- Thaila Fernanda dos Reis
- , Patrícia Alves de Castro
- & Gustavo H. Goldman
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Article
| Open AccessAssociate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens
CRISPR-regulated toxin-antitoxin (CreTA), safeguards CRISPR-Cas immune systems. Here the authors characterize a bacterial CreTA and use this to generate a proof-of-concept antimicrobial strategy, ATTACK, which associates TA and CRISPR-Cas to kill multidrug resistant pathogens.
- Rui Wang
- , Xian Shu
- & Ming Li
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Article
| Open AccessMajor proliferation of transposable elements shaped the genome of the soybean rust pathogen Phakopsora pachyrhizi
Asian soybean rust caused by Phakopsora pachyrhizi is an important plant pathogen, but an accurate genome assembly for this fungus has been lacking. This study sequenced three independent P. pachyrhizi isolates and generated reference quality assemblies and genome annotations, representing a critical step for further in-depth studies of this pathogen and the development of new methods of control.
- Yogesh K. Gupta
- , Francismar C. Marcelino-Guimarães
- & H. Peter van Esse
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Article
| Open AccessThe genomic landscape of reference genomes of cultivated human gut bacteria
Here, the authors present an expanded version of the Cultivated Genome Reference (CGR), termed CGR2, a catalog that includes 3324 high-quality draft genomes based on gut bacterial isolates from Chinese individuals, and classifies 527 species from 8 phyla, including 179 previously unidentified species, and provides information of secondary metabolite biosynthetic gene clusters and gut phage-bacteria interactions.
- Xiaoqian Lin
- , Tongyuan Hu
- & Yuanqiang Zou
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Article
| Open AccessThe evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis
Here using drug susceptibility profiling, genomics and evolutionary studies the authors provide strategies to exploit collateral drug responses in Mycobacterium tuberculosis to prevent the emergence of drug resistance.
- Natalie J. E. Waller
- , Chen-Yi Cheung
- & Matthew B. McNeil
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Article
| Open AccessEngineered hypermutation adapts cyanobacterial photosynthesis to combined high light and high temperature stress
Cyanobacteria mutants with improved tolerance to combined high light and high temperature (HLHT) are rarely reported. Here, the authors use a hypermutation system for adaptive laboratory evolution and identify a mutant with improved HLHT tolerance by enhancing expression of shikimate kinase.
- Huili Sun
- , Guodong Luan
- & Xuefeng Lu
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Article
| Open AccessMembrane-localized expression, production and assembly of Vibrio parahaemolyticus T3SS2 provides evidence for transertion
It has been proposed that bacterial membrane proteins may be produced via ‘transertion’, or concurrent transcription, translation and membrane insertion from membrane-associated genes. Here, Kaval et al. provide evidence supporting that Vibrio parahaemolyticus uses transertion to assemble a transmembrane complex (type III secretion system) used to inject virulence factors into host cells.
- Karan Gautam Kaval
- , Suneeta Chimalapati
- & Kim Orth
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Article
| Open AccessGenomic attributes of Vibrio cholerae O1 responsible for 2022 massive cholera outbreak in Bangladesh
Vibrio cholerae has undergone continuous evolution, and differing strains have caused numerous outbreaks. Here, the authors present a genomic study of Vibrio cholerae O1 responsible for a 2022 outbreak in Dhaka.
- Md Mamun Monir
- , Mohammad Tarequl Islam
- & Munirul Alam
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Article
| Open AccessHigh-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection
Here, by high-resolution SARS-CoV-2 sequencing, genomic and transcriptomic analyses from tissue samples, Normandin et al. investigate viral dynamics in fatal cases of COVID-19, revealing persistent infection in distinct anatomical sites, including the heart and testis.
- Erica Normandin
- , Melissa Rudy
- & Isaac H. Solomon
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Article
| Open AccessHost-microbe co-metabolism via MCAD generates circulating metabolites including hippuric acid
Here, using a mouse model, the authors report a previously undescribed role for medium-chain acyl-CoA dehydrogenase in host metabolism of gut microbiota metabolites, and show that circulating compounds, including the abundant organic acid hippurate, depend on host-microbe co-metabolism of phenylalanine by Clostridium sporogenes.
- Kali M. Pruss
- , Haoqing Chen
- & Dylan Dodd
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Article
| Open AccessReal-time visualisation of the intracellular dynamics of conjugative plasmid transfer
Conjugation is a contact-dependent mechanism for the transfer of plasmid DNA between bacterial cells. Here, Couturier et al. use live-cell microscopy to visualise the intracellular dynamics of conjugation in real time, revealing a molecular strategy that allows the sequential production of factors involved in establishing, maintaining and disseminating the plasmid.
- Agathe Couturier
- , Chloé Virolle
- & Christian Lesterlin
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Article
| Open AccessRapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants
Here, by sequencing viruses from individuals in multiple households, Bendall et al. find that SARS-CoV-2 transmission bottleneck does not vary between individuals infected with pre-variant lineages and those infected with highly transmissible Alpha, Delta, or Omicron variants, suggesting these tight bottlenecks will limit the spread of new mutations.
- Emily E. Bendall
- , Amy P. Callear
- & Adam S. Lauring
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Article
| Open AccessHarnessing gut microbes for glycan detection and quantification
Detecting distinct glycans within heterogeneous mixtures is hindered by glycan structural complexity and diversity. Here the authors exploit the ability of gut microbes to sense different glycan structures in order to develop quantitative glycan biosensors by coupling bacterial detection machinery to an optimised luciferase reporter.
- Jennifer L. Modesto
- , Victoria H. Pearce
- & Guy E. Townsend II
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Article
| Open AccessDeep mutational scanning of essential bacterial proteins can guide antibiotic development
Deep mutational scanning can be used to investigate protein function and stability. Here, Dewachter et al. use deep mutational scanning on three essential bacterial proteins to study the mutations’ effects in their original genomic context, providing insight into the proteins’ function and their potential as targets for new antibiotic development.
- Liselot Dewachter
- , Aaron N. Brooks
- & Jan Michiels
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Article
| Open AccessResolving colistin resistance and heteroresistance in Enterobacter species
Taxonomical complexity has muddled the classification of clinically relevant Enterobacter species. Authors carry out a genome-based study on clinical isolates to investigate colistin resistance and heteroresistance in Enterobacter.
- Swapnil Prakash Doijad
- , Nicolas Gisch
- & Trinad Chakraborty
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Article
| Open AccessAn ISO-certified genomics workflow for identification and surveillance of antimicrobial resistance
The implementation of genomics for identification and surveillance of antimicrobial resistance (AMR) in clinical laboratories remains challenging. Here, Sherry et al. present a bioinformatics platform for detection of AMR determinants from whole-genome sequencing data, suitable for clinical and public-health microbiology reporting.
- Norelle L. Sherry
- , Kristy A. Horan
- & Torsten Seemann
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Article
| Open AccessMultistep diversification in spatiotemporal bacterial-phage coevolution
Bacteria and their viruses coexist and coevolve in nature, but maintaining them together in the lab is challenging. Here, a spatially structured environment allowed prolonged coevolution, with bacteria and phage diversifying into multiple ecotypes, uncovering gene mechanisms affecting phage-bacteria interactions.
- Einat Shaer Tamar
- & Roy Kishony
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Article
| Open AccessGenome-wide identification of genes required for alternative peptidoglycan cross-linking in Escherichia coli revealed unexpected impacts of β-lactams
β-lactam-induced bacterial killing is complex and not fully resolved. Authors carry out a genome-wide analysis, through penicillin-binding protein replacement, to identify genes essential for drug efficacy.
- Henri Voedts
- , Sean P. Kennedy
- & Jean-Emmanuel Hugonnet
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Article
| Open AccessDynamics of extended-spectrum cephalosporin resistance genes in Escherichia coli from Europe and North America
Extended-spectrum cephalosporin resistance genes in Escherichia coli have spread worldwide. Here, the authors dissect the emergence and distribution of these genes over time, and across geographic location and host species, to better understand their dynamics and mechanisms of transmission.
- Roxana Zamudio
- , Patrick Boerlin
- & Alison E. Mather
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Article
| Open AccessGenetic manipulation of the human gut bacterium Eggerthella lenta reveals a widespread family of transcriptional regulators
Eggerthella lenta is a prominent human gut bacterium implicated in several physiological processes, but its study has remained limited. Here, by developing a genetic toolbox for E. lenta, the authors provide insights into how the bacterium regulates drug and dietary compound metabolism.
- Xueyang Dong
- , Ben G. H. Guthrie
- & Emily P. Balskus
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Article
| Open AccessAn RNA sponge controls quorum sensing dynamics and biofilm formation in Vibrio cholerae
Small regulatory RNAs (sRNAs) often act in concert with the RNA-chaperone Hfq to regulate the expression of multiple target transcripts in bacteria. Here, the authors identify Hfq-interacting sRNAs and their targets in the pathogen Vibrio cholerae, including an RNA sponge that binds and inactivates four sRNAs that modulate the quorum sensing pathway.
- Michaela Huber
- , Anne Lippegaus
- & Kai Papenfort
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Article
| Open AccessCharacterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial
Molnupiravir is an antiviral that forces lethal error catastrophe in SARS-CoV-2 RNAs. Here, the authors confirm the mechanism of action of molnupiravir in humans using samples obtained from the UK’s AGILE phase IIa clinical trial investigating the antiviral efficacy of the drug against SARS-CoV-2. No treatment-associated SARS-CoV-2 mutations were identified.
- I’ah Donovan-Banfield
- , Rebekah Penrice-Randal
- & Thomas Fletcher
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Article
| Open AccessVarying strength of selection contributes to the intragenomic diversity of rRNA genes
Ribosomal RNA genes are abundant in eukaryotic genomes and code for the universal and essential RNA components of the ribosome. This study uncovers high sequence diversity of the genes within a single species and discusses the contribution of selection in the evolution of ribosomal RNA.
- Daniel Sultanov
- & Andreas Hochwagen
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Article
| Open AccessA comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome
H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome is the reference sequence for this pathogen. Here, Chitale et al. present a bioinformatic pipeline for accurate assembly of bacterial genome sequences, and use it to provide important updates to the M. tuberculosis reference genome.
- Poonam Chitale
- , Alexander D. Lemenze
- & David Alland
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Article
| Open AccessPromiscuity of response regulators for thioredoxin steers bacterial virulence
The response regulator SsrB, a master activator of the Salmonella pathogenicity island-2 gene cluster, is under allosteric control of thioredoxin. Authors utilise in vitro and in vivo models to investigate if other members of the response regulator family might have adopted thioredoxin as a regulator.
- Ju-Sim Kim
- , Alexandra Born
- & Andrés Vázquez-Torres
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Article
| Open AccessGenome-centric analysis of short and long read metagenomes reveals uncharacterized microbiome diversity in Southeast Asians
Reference genomes for gut microbiomes help unravel microbial “dark matter” and serve as valuable resource for disease-focused studies. Here, the authors perform short and long read metagenomics and metagenome-assembled genomes analyses to profile the gut microbiome of Southeast Asian populations, revealing significant species and strain-level diversity, with thousands of previously uncharacterized biosynthetic gene clusters.
- Jean-Sebastien Gounot
- , Minghao Chia
- & Niranjan Nagarajan
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Article
| Open AccessExperimental validation that human microbiome phages use alternative genetic coding
Previous bioinformatic analyses have indicated that bacteriophages can use genetic codes different from those of their host bacteria. Here, Peters et al. use metaproteomics to provide experimental evidence of reassignment of stop codon TAG to glutamine in phages found in the human gut microbiome.
- Samantha L. Peters
- , Adair L. Borges
- & Robert L. Hettich
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Article
| Open AccessPredicting the evolution of the Lassa virus endemic area and population at risk over the next decades
It is currently unknown how climate and land use changes could affect the endemic area of Lassa virus, a zoonotic pathogen responsible for Lassa fever. Here, the authors show that by 2070, new regions in Africa will likely become ecologically suitable for Lassa virus, drastically increasing the population living in conditions favourable for virus circulation.
- Raphaëlle Klitting
- , Liana E. Kafetzopoulou
- & Simon Dellicour
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Article
| Open AccessMcaA and McaB control the dynamic positioning of a bacterial magnetic organelle
Magnetotactic bacteria use intracellular chains of ferrimagnetic nanocrystals, produced within magnetosome organelles, to align and navigate along the geomagnetic field. Here, Wan et al. identify two proteins involved in magnetosome positioning in Magnetospirillum magneticum, homologs of which are widespread among magnetotactic bacteria.
- Juan Wan
- , Caroline L. Monteil
- & Arash Komeili
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Article
| Open AccessAn online atlas of human plasma metabolite signatures of gut microbiome composition
Here, Dekkers et al. characterize associations of 1528 gut metagenomic species with the plasma metabolome in 8583 participants of the SCAPIS Study, and find that gut microbiota explain up to 58% of the variance of individual plasma metabolites.
- Koen F. Dekkers
- , Sergi Sayols-Baixeras
- & Tove Fall
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Article
| Open AccessStructural characterization of a soil viral auxiliary metabolic gene product – a functional chitosanase
Metagenomics is revealing auxiliary metabolic genes (AMGs) in soil viral genomes. Here, authors solve the crystal structure for a soil viral AMG product, free and ligand bound, and show the protein can decompose chitin, a common carbon polymer.
- Ruonan Wu
- , Clyde A. Smith
- & Janet K. Jansson
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Article
| Open AccessTranscontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis
An outbreak of the multidrug-resistant Mycobacterium tuberculosis lineage W148 has spread widely across Russia, Central Asia and Europe. Here, the authors use whole genome sequences of ~700 isolates of this lineage collected over ~20 years to analyze its spread, evolution of drug resistance, and impact of compensatory mutations.
- Matthias Merker
- , Jean-Philippe Rasigade
- & Thierry Wirth
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Article
| Open AccessRapid evolution of mutation rate and spectrum in response to environmental and population-genetic challenges
How rapidly the mutation rate responds evolutionarily to ecological and population-genetic factors over time is unclear. Here, the authors show that the evolution of mutation rates in E. coli proceeds rapidly in response to these factors with substantial bidirectional shifts.
- Wen Wei
- , Wei-Chin Ho
- & Michael Lynch
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Article
| Open AccessAdaptation to novel spatially-structured environments is driven by the capsule and alters virulence-associated traits
Phenotypic and genotypic evolution in worrisome Klebsiella spp. is influenced by the capsule. Here the authors show that adaptation outside the host can impact virulence-associated traits, including de novo emergence of hypermucoviscosity.
- Amandine Nucci
- , Eduardo P. C. Rocha
- & Olaya Rendueles
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Article
| Open AccessCombined comparative genomics and clinical modeling reveals plasmid-encoded genes are independently associated with Klebsiella infection
Patient variables, such as comorbidities, partially explain which patients will progress to Klebsiella infection, with colonization of the gut acting as a reservoir. Little is known, however, regarding Klebsiella genes that may increase risk of disease in colonized individuals. Here, authors conduct a comparative genomics study to identify genes associated with progression from colonisation to infection.
- Jay Vornhagen
- , Emily K. Roberts
- & Michael A. Bachman
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Article
| Open AccessDevelopment of a novel core genome MLST scheme for tracing multidrug resistant Staphylococcus capitis
Staphylococcus capitis is a common causative agent of bloodstream infections in neonatal intensive care units, with multidrug resistant isolates complicating treatment. Authors aimed to establish a core genome multilocus sequence typing (cgMLST) scheme to document the transmission and dissemination of multidrug-resistant S. capitis isolates.
- Zhengan Wang
- , Chao Gu
- & Yunsong Yu
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Article
| Open AccessPopulation genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion
Group B Streptococcus (GBS) causes neonatal disease and mortality worldwide. Here, the authors use genome-wide association analyses to identify bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease.
- Chrispin Chaguza
- , Dorota Jamrozy
- & Stephen D. Bentley
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Article
| Open AccessGenomic epidemiology of Delta SARS-CoV-2 during transition from elimination to suppression in Aotearoa New Zealand
Aotearoa New Zealand pursued a COVID-19 elimination strategy until October 2021 when it moved to a suppression strategy. In this genomic surveillance study, the authors describe spread of the virus during the transition between these strategies, with evidence of substantial undetected community transmission.
- Lauren Jelley
- , Jordan Douglas
- & Jemma L. Geoghegan
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Article
| Open AccessA plasmid system with tunable copy number
The range of available copy numbers for cloning vectors is largely restricted to the handful of ORIs that have been isolated from plasmids found in nature. Here the authors introduce a plasmid system that allow for the continuous, finely-tuned control of plasmid copy number between 1 and 800 copies per cell.
- Miles V. Rouches
- , Yasu Xu
- & Guillaume Lambert
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Article
| Open AccessA comprehensive resource for Bordetella genomic epidemiology and biodiversity studies
The genus Bordetella includes environmental bacteria as well as human pathogens. Here, the authors present a large database of environmental and clinical Bordetella isolates and genome sequences, and develop genotyping systems to facilitate evolutionary and epidemiological studies.
- Sébastien Bridel
- , Valérie Bouchez
- & Sylvain Brisse
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Article
| Open AccessRNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3′UTR required for intermediate vancomycin resistance
Regulatory small RNA (sRNA) interact with mRNAs to regulate their stability, transcription, and translation via diverse mechanisms. Here, Mediati et al. apply RNase III-CLASH to multidrug-resistant Staphylococcus aureus to characterise the network of RNA–RNA interactions associated with RNase III and identify a regulatory mRNA 3′UTR, named vigR-3′UTR, involved in the regulation of genes relevant for vancomycin sensitivity.
- Daniel G. Mediati
- , Julia L. Wong
- & Jai J. Tree
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Article
| Open AccessBifurcation drives the evolution of assembly-line biosynthesis
Reprogramming biosynthetic assembly-lines is a topic of interest for antibiotics. Here, the authors explore the evolutionary biosynthesis of anti-tubercular wollamides, show gene duplication and neo-functionalisation results in bifurcation allowing for testing of new structures with the ability to recover old structures by gene loss.
- Thomas J. Booth
- , Kenan A. J. Bozhüyük
- & Barrie Wilkinson
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Article
| Open AccessShort- and long-read metagenomics expand individualized structural variations in gut microbiomes
Here, Wang and colleagues combine short and long sequencing reads to characterize structural variations, prophage and CRISPR spacer elements in human gut microbiomes, and reveal functional differences at a finer level of bacterial strains.
- Liang Chen
- , Na Zhao
- & Jun Wang
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Article
| Open AccessA genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance
A lack of understanding in the development and emergence of antimicrobial resistance presents as a problem for accurate infection diagnosis and treatment. Here, authors utilize Streptococcus pneumoniae and build a genome-wide atlas to understand the genes and interactions that contribute to altered drug susceptibility.
- Dmitry Leshchiner
- , Federico Rosconi
- & Tim van Opijnen
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Article
| Open AccessFrequency modulation of a bacterial quorum sensing response
Quorum-sensing bacteria produce and secrete autoinducers that trigger a behavioral change in the population when reaching a certain threshold. Here, Bettenworth et al. show that autoinducer synthase gene expression in Sinorhizobium meliloti occurs in asynchronous stochastic pulses, and that physiological cues modulate pulse frequency and, consequently, response behavior dynamics. Frequency-modulated pulsing in autoinducer synthase gene expression thus represents a time-based mechanism for information integration and collective decision-making.
- Vera Bettenworth
- , Simon van Vliet
- & Anke Becker
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Article
| Open AccessElimination of human rabies in Goa, India through an integrated One Health approach
Dog vaccination is an effective rabies prevention measure, but widespread vaccination campaigns are challenging in settings like India with large free-roaming dog populations. Here, the authors describe a One Health campaign in Goa state which led to a large reduction of cases in dogs and elimination in humans.
- A. D. Gibson
- , G. Yale
- & R. J. Mellanby
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Article
| Open AccessCo-infection with SARS-CoV-2 Omicron and Delta variants revealed by genomic surveillance
Here, using genomic approaches, Rockett et al. identify Omicron and Delta SARS-CoV-2 co-infections in two adults, highlighting the usefulness of genomic surveillance for the timely recognition of co-infections in situations when different variants of the virus are circulating in the community.
- Rebecca J. Rockett
- , Jenny Draper
- & Vitali Sintchenko
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Article
| Open AccessUnlocking the functional potential of polyploid yeasts
Domesticated industrial yeast strains are sterile, which hampers to breed strains with novel properties. Here, the authors employ the genetics paradigm return-to-growth to induce genome wide recombination in two sterile polyploid industrial yeasts and identify clones with superior biotechnological traits.
- Simone Mozzachiodi
- , Kristoffer Krogerus
- & Gianni Liti