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Genomic language model predicts protein co-regulation and function
A gene’s function is governed by its sequence, structure and context. Here, the authors develop a genomic language model that learns contextualized functional representations from diverse and large-scale metagenomic datasets.
- Yunha Hwang
- , Andre L. Cornman
- & Peter R. Girguis
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Early detection of emerging viral variants through analysis of community structure of coordinated substitution networks
Rise of new viral strains is a major public health challenge, demanding advanced detection and forecasting methods. This study shows how examining communities within networks of viral mutations enables early detection of emerging strains.
- Fatemeh Mohebbi
- , Alex Zelikovsky
- & Pavel Skums
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Article
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Transcription-driven DNA supercoiling counteracts H-NS-mediated gene silencing in bacterial chromatin
Proteins compacting the bacterial chromosome obstruct transcription and must be transiently displaced to allow gene expression. Here, the authors show that the bacterial nucleoid structuring protein H-NS can be dislodged, from a distance, by the twisting in the DNA generated ahead of approaching RNA polymerase.
- Nara Figueroa-Bossi
- , Rocío Fernández-Fernández
- & Lionello Bossi
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Real-time monitoring of replication errors’ fate reveals the origin and dynamics of spontaneous mutations
An interdisciplinary approach following replication errors in Escherichia coli unveils that many spontaneous mutations originate from inefficient repair, and that repair capacity is variable between single cells within a bacterial population.
- Chiara Enrico Bena
- , Jean Ollion
- & Marina Elez
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Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus
The impact of other pathogens on disease outcome was studied in European infants with RSV infection. Additional viruses were commonly co-detected during infection but were weakly linked to severity. However, presence of Haemophilus bacteria strongly associated with severe cases.
- Gu-Lung Lin
- , Simon B. Drysdale
- & Andrew J. Pollard
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Characterisation of colistin resistance in Gram-negative microbiota of pregnant women and neonates in Nigeria
Here, the authors report the results of a BARNARDS sub-study identifying a 1% mobile colistin resistance gene (mcr) carriage rate in around 5000 rectal swabs from mothers and neonates across Nigeria, of which 90% were mcr-10 (mostly Enterobacter spp.) and 10% were mcr-1 and mcr9.
- E. A. R. Portal
- , K. Sands
- & O. B. Spiller
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Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis
Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection closely related to Streptococcus pyogenes. Here the authors investigate the degree of genomic similarity between the two species and assess implications for development of vaccines.
- Ouli Xie
- , Jacqueline M. Morris
- & Mark R. Davies
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Dependency on host vitamin B12 has shaped Mycobacterium tuberculosis Complex evolution
Campos-Pardos et al show that the virulence of Mycobacterium tuberculosis is dependent on sufficient uptake of exogenous vitamin B12 from host serum and this phenotype is not conserved in environmental, opportunistic and ancestral lineages.
- Elena Campos-Pardos
- , Santiago Uranga
- & Jesús Gonzalo-Asensio
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bacLIFE: a user-friendly computational workflow for genome analysis and prediction of lifestyle-associated genes in bacteria
Many bacteria live in close association with eukaryotic hosts, exhibiting detrimental, neutral or beneficial effects on host growth and health. Here, the authors present a streamlined computational workflow for bacterial genome annotation, large-scale comparative genomics, and prediction of genes potentially involved in niche adaptation.
- Guillermo Guerrero-Egido
- , Adrian Pintado
- & Víctor J. Carrión
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Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency
Bacterial capsules provide protection against the environment, including host immune systems. Authors swap capsule loci in Klebsiella pneumoniae to reveal the role of these sugar coats against plasmid conjugation and phage infection, showing that the serotype is a key player in regulating conjugation rates, and phage susceptibility.
- Matthieu Haudiquet
- , Julie Le Bris
- & Olaya Rendueles
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Transmission and dynamics of mother-infant gut viruses during pregnancy and early life
Gut ecosystem colonization impacts lifelong health. Here, authors track mother-infant gut viruses over time, reveal feeding’s influence on early viral colonization, and demonstrate the co-transmission of bacteriophages and bacteria from mothers to infants.
- Sanzhima Garmaeva
- , Trishla Sinha
- & Alexandra Zhernakova
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Quantitative pathogenicity and host adaptation in a fungal plant pathogen revealed by whole-genome sequencing
The understanding of pathogenicity in quantitative plant pathosystems remains limited. This study reveals the genetic architecture of quantitative pathogenicity traits in a significant fungal plant pathogen, shedding light on potential evolutionary mechanisms involved in host adaptation.
- Reda Amezrou
- , Aurélie Ducasse
- & Thierry C. Marcel
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Protein NirP1 regulates nitrite reductase and nitrite excretion in cyanobacteria
Some cyanobacteria excrete nitrite when the supply of inorganic carbon is limiting, but the underlying mechanisms are unclear. Here, Kraus et al. identify a conserved protein that interacts with nitrite reductase, thus regulating nitrogen metabolism and promoting nitrite excretion.
- Alexander Kraus
- , Philipp Spät
- & Wolfgang R. Hess
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The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies
Plasmids carry antimicrobial resistance genes and contribute to the rapid dissemination of resistance. Here, the authors sequence 1,880 complete plasmids from 738 isolates from bloodstream infections, shedding light on the links between plasmid types, bacterial hosts and antimicrobial resistance.
- Samuel Lipworth
- , William Matlock
- & Nicole Stoesser
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Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria
Mobile genetic elements can promote the duplication of antibiotic resistance genes which may in turn accelerate the evolution of resistance to new drugs. Here, the authors show that duplicated antibiotic resistance genes are enriched in bacterial isolates from environments associated with rampant antibiotic use.
- Rohan Maddamsetti
- , Yi Yao
- & Lingchong You
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Regulation of TRI5 expression and deoxynivalenol biosynthesis by a long non-coding RNA in Fusarium graminearum
The fungus Fusarium graminearum produces a toxin, deoxynivalenol (DON), that can be found in cereal grains and processed food or feed. Here, Huang et al. study the regulation of DON biosynthesis and show that transcription factors TRI6 and TRI10 regulate each other’s expression and that of a long non-coding RNA which, in turn, downregulates a DON biosynthesis gene.
- Panpan Huang
- , Xiao Yu
- & Cong Jiang
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Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda’s fitness landscape and enables speciation
Niche theory is often invoked to explain biodiversity, but it does not explain how species evolve to exploit unique niches. Using a combination of experimental and computational approaches, this study shows that resource competition can deform fitness landscapes, opening new pathways that promote ecological speciation.
- Michael B. Doud
- , Animesh Gupta
- & Justin R. Meyer
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Transgenic expression of cif genes from Wolbachia strain wAlbB recapitulates cytoplasmic incompatibility in Aedes aegypti
The Wolbachia cifA and cifB genes generate cytoplasmic incompatibility (CI) in insect hosts but the role of cifA is still debated. Here, the authors report the transgenic recapitulation of CI in the major arbovirus vector Aedes aegypti and provide evidence for cifA inhibiting cifB toxicity in the male germline.
- Cameron J. McNamara
- , Thomas H. Ant
- & Steven P. Sinkins
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BacPE: a versatile prime-editing platform in bacteria by inhibiting DNA exonucleases
Prime editing in bacteria is currently inefficient. Here the authors report BacPE, a versatile prime editing platform in Escherichia coli that works by inhibiting 3′→5′ DNA exonucleases, highlighting the intrinsic genetic factors that are adverse to efficient prime editing.
- Hongyuan Zhang
- , Jiacheng Ma
- & Quanjiang Ji
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Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing
Non-malarial febrile illnesses have a range of potential aetiologies which are difficult to diagnose and therefore treat. Here, the authors investigate the causes of acute febrile illness in a peri-urban area of Senegal with low malaria incidence using untargeted and targeted sequencing methods.
- Zoë C. Levine
- , Aita Sene
- & Katherine J. Siddle
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Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach
Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.
- Ivan Barilar
- , Simone Battaglia
- & Baoli Zhu
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Commensal lifestyle regulated by a negative feedback loop between Arabidopsis ROS and the bacterial T2SS
The plant immune output reactive oxygen species tames a detrimental bacterial commensal from native microbiota by suppressing a bacterial secretion system, allowing the co-existence and turning it into a beneficial bacterium to the host.
- Frederickson Entila
- , Xiaowei Han
- & Kenichi Tsuda
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CRISPR-Cas-based identification of a sialylated human milk oligosaccharides utilization cluster in the infant gut commensal Bacteroides dorei
Human milk oligosaccharides (HMOs) utilization by Bacteroides species remains poorly understood. Here, the authors describe a single specific gene cluster responsible for sialylated HMOs utilization in a B. dorei natural isolate and prove its functionality in vivo using CRISPR-Cas12a.
- Sivan Kijner
- , Dena Ennis
- & Moran Yassour
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Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection
Aspergillus fumigatus produces the mycotoxin gliotoxin which is important for virulence. Here, de Castro et al characterise how excess production and subsequent fungal toxicity is controlled by the mitogen-activated protein kinase MpkA.
- Patrícia Alves de Castro
- , Camila Figueiredo Pinzan
- & Gustavo H. Goldman
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The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomes
The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.
- Kaisa Thorell
- , Zilia Y. Muñoz-Ramírez
- & Charles S. Rabkin
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In vivo RNA interactome profiling reveals 3’UTR-processed small RNA targeting a central regulatory hub
Here the authors report a new approach to profile RNA-RNA interactions in live bacterial cells. The charted RNA interaction networks unveil a key mRNA regulatory hub targeted by twelve small RNAs, including a novel RNA involved in fatty acid metabolism.
- Fang Liu
- , Ziying Chen
- & Yanjie Chao
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Quorum-sensing synthase mutations re-calibrate autoinducer concentrations in clinical isolates of Pseudomonas aeruginosa to enhance pathogenesis
Simanek et al. discovered variants that arise in the protein responsible for synthesizing a molecule required for bacterial communication, which mediates the progression of virulence in the pathogen Pseudomonas aeruginosa.
- Kayla A. Simanek
- , Megan L. Schumacher
- & Jon E. Paczkowski
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TRS: a method for determining transcript termini from RNAtag-seq sequencing data
TRS is a new method for determining 3’ transcript termini in bacteria, using data generated by the RNAtag-seq protocol. This methodology opens the door to study the evolution of transcription termini and their condition-dependent dynamics.
- Amir Bar
- , Liron Argaman
- & Hanah Margalit
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The genomic epidemiology of shigellosis in South Africa
As a leading cause of diarrhoeal mortality and morbidity, authors examine the epidemiology and genome dynamics of shigellosis in South Africa, utilising whole genome sequence analysis.
- George E. Stenhouse
- , Karen H. Keddy
- & Kate S. Baker
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Distributed genotyping and clustering of Neisseria strains reveal continual emergence of epidemic meningococcus over a century
Core genome multilocus sequence typing (cgMLST) is used to classify bacterial strains for epidemiological applications. Here, the authors describe a distributed cgMLST scheme that does not require a central database of allelic sequences, and apply it to study evolutionary patterns of epidemic and endemic strains of the genus Neisseria.
- Ling Zhong
- , Menghan Zhang
- & Zhemin Zhou
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Global pathogenomic analysis identifies known and candidate genetic antimicrobial resistance determinants in twelve species
A global analysis of antimicrobial resistance (AMR) across 27,155 genomes and 69 drugs reveals patterns in AMR gene transfer between species and identifies 142 AMR gene candidates, two of which were tested and confirmed as contributing to AMR.
- Jason C. Hyun
- , Jonathan M. Monk
- & Bernhard O. Palsson
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Regulation of the physiology and virulence of Ralstonia solanacearum by the second messenger 2′,3′-cyclic guanosine monophosphate
Nucleotide second messengers are employed by many bacterial species to regulate various cellular processes. Here, the authors demonstrate that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions and virulence in Ralstonia solanacearum by abolishing the interaction between a transcriptional regulator and the promoters of target genes.
- Xia Li
- , Wenfang Yin
- & Yinyue Deng
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The heat shock protein LarA activates the Lon protease in response to proteotoxic stress
The Lon protease is an important protein degradation machine and is conserved across the three domains of life. Here, the authors describe a small proteotoxic stress-induced protein that functions as an allosteric activator of Lon.
- Deike J. Omnus
- , Matthias J. Fink
- & Kristina Jonas
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High-resolution temporal profiling of E. coli transcriptional response
Understanding how cells dynamically adapt to their environment is important, but temporal information about cellular behaviour is often limited. Here, Miano et al. apply unsupervised machine learning to a dataset describing the activity of over 1,800 promoters in E. coli, measured every 10 minutes, defining three primary stages of promoter activation in response to heavy metal stress.
- Arianna Miano
- , Kevin Rychel
- & Jeff Hasty
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Direct comparison of spatial transcriptional heterogeneity across diverse Bacillus subtilis biofilm communities
The bacterium Bacillus subtilis can form various types of surface-associated communities, such as colonies, pellicles and submerged biofilms. Here, Dergham et al. provide a direct comparison of spatial transcriptional heterogeneity across the three types of surface-associated communities, revealing mosaic expression patterns for genes involved in various pathways.
- Yasmine Dergham
- , Dominique Le Coq
- & Romain Briandet
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A smooth tubercle bacillus from Ethiopia phylogenetically close to the Mycobacterium tuberculosis complex
The Mycobacterium tuberculosis complex (MTBC) includes several pathogens thought to have originated in East Africa from an ancestor closely related to Mycobacterium canettii. Here, the authors describe a clinical tuberculosis strain isolated in Ethiopia that has typical M. canettii features but is phylogenetically much closer to the MTBC clade, supporting that the emergence of MTBC pathogens is a recent evolutionary event.
- Bazezew Yenew
- , Arash Ghodousi
- & Daniela Maria Cirillo
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c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
H-NS is a global regulatory protein that represses expression of many genes in bacteria. Here, Li et al. show that a second messenger, cyclic di-GMP, binds to H-NS and inhibits its binding to DNA, thus relieving H-NS-mediated transcriptional silencing.
- Shuyu Li
- , Qinmeng Liu
- & Lei Zhang
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Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions
Here, Rueff et al engineered a CRISPRi-based oscillator to rewire capsule production in Streptococcus pneumoniae from its native control. They show that heterogeneity in capsule production is beneficial for fitness in several virulence associated traits.
- Anne-Stéphanie Rueff
- , Renske van Raaphorst
- & Jan-Willem Veening
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The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi
Pneumococcal vaccination has been shown to promote emergence of non-vaccine S. pneumoniae serotypes. Here, the authors use data from Malawi to investigate whether vaccine introduction also results in changes in metabolic, virulence, and antimicrobial resistance profiles of circulating strains.
- Uri Obolski
- , Todd D. Swarthout
- & Robert S. Heyderman
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Gut microbial structural variation associates with immune checkpoint inhibitor response
Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, the authors characterize gut microbial genomic structural variants, located in species such as Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae, that associate with hosts’ response and survival after immune checkpoint inhibitors treatment.
- Rong Liu
- , You Zou
- & Dao-Ming Wang
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Article
| Open Access
Fungal secondary metabolism is governed by an RNA-binding protein CsdA/RsdA complex
RsdA regulates the secondary metabolism in fungi. Here the authors show that RNA-binding protein CsdA interacts with RsdA protein and regulates expression of RsdA, coordinating secondary metabolism in fungi.
- Zili Song
- , Shuang Zhou
- & Wen-Bing Yin
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Article
| Open Access
Clinically relevant antibiotic resistance genes are linked to a limited set of taxa within gut microbiome worldwide
Antimicrobial resistance genes (ARGs) in commensal gut bacteria may act as a reservoir for acquisition by pathogens. Here, the authors assess the distribution and transfer potential of ARGs in gut microbiomes and find that clinically important ARGs are taxonomically restricted despite being associated with mobile plasmids
- Peter J. Diebold
- , Matthew W. Rhee
- & Ilana L. Brito
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Essential gene complement of Planctopirus limnophila from the bacterial phylum Planctomycetes
Bacteria of the phylum Planctomycetes display unique cell biology features but are relatively understudied. Here, the authors report a genome-wide analysis of essential gene content in a planctomycete, providing insights into the divergent molecular and cell biology of these organisms.
- Elena Rivas-Marin
- , David Moyano-Palazuelo
- & Damien P. Devos
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Co-option of a non-retroviral endogenous viral element in planthoppers
Non-retroviral endogenous viral elements are widely dispersed in eukaryotic genomes, but their functions remain largely unknown. Here, Huang et al show that one such element in planthoppers has been co-opted and contributes to insect fitness..
- Hai-Jian Huang
- , Yi-Yuan Li
- & Jun-Min Li
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Article
| Open Access
Mutational spectra are associated with bacterial niche
Mutagens and DNA repair defects generate context-specific mutational signatures in cancer cells. Here, Ruis et al. provide evidence of similar processes in bacteria, showing that mutational spectra may be associated with sites of bacterial replication when mutagen exposures differ, and can be used in these cases to infer transmission routes.
- Christopher Ruis
- , Aaron Weimann
- & Julian Parkhill
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Article
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Diagnostic and commensal Staphylococcus pseudintermedius genomes reveal niche adaptation through parallel selection of defense mechanisms
Staphylococcus pseudintermedius has a wide host-range in domesticated and wild animals, yet it has also been isolated as an opportunistic pathogen in human wounds. In this work, the authors genotypically analyse S. pseudintermedius isolates from veterinary diagnostic laboratories and medical care centres, alongside household surfaces and inhabitants.
- Sanjam S. Sawhney
- , Rhiannon C. Vargas
- & Gautam Dantas
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Catalytically inactive long prokaryotic Argonaute systems employ distinct effectors to confer immunity via abortive infection
Here, Song et al. show that catalytically inactive long prokaryotic Argonaute proteins are equipped with distinct effectors that are activated upon recognition of invading genetic elements to trigger cell death and confer abortive infection immunity.
- Xinmi Song
- , Sheng Lei
- & Wenyuan Han
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Article
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Inferring bacterial transmission dynamics using deep sequencing genomic surveillance data
Studying rare genetic changes that arose as an infectious bacterium spread between lab mice, here the authors show that using the relative abundance of any changes rather than just whether they occurred can more precisely identify who likely infected who.
- Madikay Senghore
- , Hannah Read
- & Siouxsie Wiles
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| Open Access
Origin of fungal hybrids with pathogenic potential from warm seawater environments
Most clinical isolates of the pathogenic yeast Candida orthopsilosis are hybrids of two parental lineages, only one of which has been identified. Here, del Olmo et al. show that C. orthopsilosis strains isolated from warm seawater are hybrids closely related to clinical isolates, and identify the missing parental lineage, thus providing a more complete view of the genomic evolution of this species.
- Valentina del Olmo
- , Verónica Mixão
- & Toni Gabaldón
All-inclusive nitrifiers in Antarctic soils