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| Open AccessCrystal structure and functional implications of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases
Here, the authors present structural and functional characterization of bacterial CD-NTases that synthesize cyclic dipyrimidines for phage resistance, revealing a (R/Q)xW motif dictating pyrimidine selection which suggests a sequential pathway for synthesizing 2’3’-cyclic di-UMP.
- Chia-Shin Yang
- , Tzu-Ping Ko
- & Yeh Chen
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Article
| Open AccessThe RIX domain defines a class of polymorphic T6SS effectors and secreted adaptors
Bacteria use the type VI secretion system (T6SS) to deliver toxic effectors into bacterial or eukaryotic cells. Here, Kanarek et al. identify a protein domain, RIX, that defines a class of polymorphic T6SS effectors with antibacterial and anti-eukaryotic toxic domains, and that enables T6SS-mediated delivery of other effectors.
- Katarzyna Kanarek
- , Chaya Mushka Fridman
- & Dor Salomon
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Article
| Open AccessHigh resolution cryo-EM and crystallographic snapshots of the actinobacterial two-in-one 2-oxoglutarate dehydrogenase
The 2-oxoglutarate dehydrogenase complex (ODH) is a textbook example of multienzymatic machinery. Here, the authors report the structural and regulatory properties of the Actinobacterial enzyme OdhA, a fusion of two ODH components acting in a supercomplex with pyruvate dehydrogenase.
- Lu Yang
- , Tristan Wagner
- & Marco Bellinzoni
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Matters Arising
| Open AccessReply to: Antibiotics and hexagonal order in the bacterial outer membrane
- Selen Manioglu
- , Seyed Majed Modaresi
- & Sebastian Hiller
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Article
| Open AccessProfiling cell envelope-antibiotic interactions reveals vulnerabilities to β-lactams in a multidrug-resistant bacterium
The bacterial pathogen Burkholderia cenocepacia and related species are often multidrug resistant because their cell envelope restricts antibiotic penetration. Here, Hogan et al systematically identify genes associated with resistance and susceptibility to cell envelope-targeting antibiotics, providing insights into underlying mechanisms and suggesting avenues for development of improved antibacterial therapies.
- Andrew M. Hogan
- , A. S. M. Zisanur Rahman
- & Silvia T. Cardona
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Article
| Open AccessBtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B12 uptake in gut Bacteroides
Uptake of vitamin B12 is important for colonisation of the gut by Bacteroides species. Here the authors characterise B12 uptake in Bacteroides thetaiotaomicron, mediated by outer membrane protein complexes consisting of surface-exposed BtuG lipoproteins and BtuB TonB-dependent transporters.
- Javier Abellon-Ruiz
- , Kalyanashis Jana
- & Bert van den Berg
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Article
| Open AccessConformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
The divisome is a macromolecular machine composed of more than 30 proteins that controls cell wall constriction during bacterial cell division. Here, the authors provide insights into the structure and dynamics of the divisome core complex using a combination of structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis.
- Brooke M. Britton
- , Remy A. Yovanno
- & Zach Hensel
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Article
| Open AccessIon selectivity and rotor coupling of the Vibrio flagellar sodium-driven stator unit
In this work, the authors provide mechanistic insights for understanding the sodium-dependent, bacterial flagellar stator unit PomAB ion selectivity, directional rotation, and rotor incorporation in Vibrio spp.
- Haidai Hu
- , Philipp F. Popp
- & Nicholas M. I. Taylor
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Article
| Open AccessSequestration of histidine kinases by non-cognate response regulators establishes a threshold level of stimulation for bacterial two-component signaling
Bacterial two-component systems consist of a sensor histidine kinase (HK) that perceives a signal, and a cognate response regulator (RR) that modulates target gene expression. Here, the authors combine experiments and mathematical modelling to show that phosphorylated HKs can be sequestered by non-cognate RRs, which prevents responses to weak signals.
- Gaurav D. Sankhe
- , Rubesh Raja
- & Deepak Kumar Saini
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Article
| Open AccessHerbarium specimen sequencing allows precise dating of Xanthomonas citri pv. citri diversification history
Herbarium collections are an important source of historical DNA, whose analysis can shed light on the evolutionary history of plant pathogens. Here, Campos et al. reconstruct historical genomes of the bacterial crop pathogen Xanthomonas citri pv. citri from citrus herbarium specimens, estimating that the pathogen originated in Southern Asia ~11,500 years ago and diversified during the beginning of the 13th century.
- Paola E. Campos
- , Olivier Pruvost
- & Lionel Gagnevin
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Article
| Open AccessInsertion sequence transposition inactivates CRISPR-Cas immunity
CRISPR-Cas immunity systems safeguard prokaryotic genomes by inhibiting the invasion of mobile genetic elements. Here, the authors show that insertion sequences can efficiently insert into cas genes, thus inactivating CRISPR defenses and increasing bacterial susceptibility to foreign DNA invasion.
- Yong Sheng
- , Hengyu Wang
- & Qianjin Kang
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Article
| Open AccessIdentification of a deep-branching thermophilic clade sheds light on early bacterial evolution
Thermophilic microorganisms can live at high temperatures, but the origin and evolution of this ability are unclear. Here, the authors isolate a thermophilic bacterium from a deep-sea hydrothermal vent, and show it belongs to a major early-diverging lineage whose ancestor was likely also a thermophilic bacterium.
- Hao Leng
- , Yinzhao Wang
- & Xiang Xiao
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Article
| Open AccessAcquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella
The bacterial genus Kingella includes pathogenic species that secrete a toxin called RtxA, which is absent in commensal species. Here, Morreale et al. identify key steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer of the toxin-encoding genes, co-option of an existing secretion system, and gene duplication.
- Daniel P. Morreale
- , Eric A. Porsch
- & Paul J. Planet
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Article
| Open AccessMolecular basis of β-lactam antibiotic resistance of ESKAPE bacterium E. faecium Penicillin Binding Protein PBP5
Penicillin Binding Proteins (PBPs) are the main targets of β-lactam antibiotics. Here the authors use NMR spectroscopy, crystallography and microbiology to define the dynamics of E. faecium PBP5 in solution and show that increased acyl-enzyme hydrolysis correlates with increased resistance.
- Yamanappa Hunashal
- , Ganesan Senthil Kumar
- & Wolfgang Peti
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Article
| Open AccessGenetic strategies for sex-biased persistence of gut microbes across human life
Here, via analyses of shotgun metagenomic sequencing data of more than 12,000 fecal microbiomes from healthy individuals, the authors reveal the presence of microbiome genetic traits involved in host mucin metabolism, supporting colonization and persistence of specific bacterial strains preferentially in the intestinal environment of women compared to men.
- Chiara Tarracchini
- , Giulia Alessandri
- & Marco Ventura
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Article
| Open AccessFunctional decomposition of metabolism allows a system-level quantification of fluxes and protein allocation towards specific metabolic functions
Quantifying the contribution of individual molecular components to complex cellular processes is a grand challenge in systems biology. Here, the authors present a general theoretical framework (Functional Decomposition of Metabolism, FDM) to quantify the contribution of every metabolic reaction to metabolic functions, e.g. the synthesis of biomass building blocks.
- Matteo Mori
- , Chuankai Cheng
- & Terence Hwa
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Article
| Open AccessDecoding a cryptic mechanism of metronidazole resistance among globally disseminated fluoroquinolone-resistant Clostridioides difficile
Detection of resistance to the antibiotic metronidazole in C. difficile often requires the presence of heme in the media, for unclear reasons. Here, the authors show that most metronidazole-resistant strains carry a mutation that promotes expression of a heme-dependent enzyme that degrades nitroimidazoles, and the mutation often co-occurs with an amino-acid substitution in DNA gyrase that confers resistance to another class of antibiotics, fluoroquinolones.
- Abiola O. Olaitan
- , Chetna Dureja
- & Julian G. Hurdle
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Article
| Open AccessOn the mechanisms of lysis triggered by perturbations of bacterial cell wall biosynthesis
Inhibition of bacterial cell wall synthesis by β-lactam antibiotics results in a loss of cell wall integrity, but cells die via a combination of downstream events involving metabolic perturbations and oxidative damage. Here, Kawai et al. identify key enzymatic steps that stimulate the generation of reactive oxygen species and highlight the role of iron homeostasis in the lethal effects mediated by oxidative damage.
- Yoshikazu Kawai
- , Maki Kawai
- & Jeff Errington
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Article
| Open AccessDipM controls multiple autolysins and mediates a regulatory feedback loop promoting cell constriction in Caulobacter crescentus
Proteins with a catalytically inactive LytM-type endopeptidase domain regulate cell wall-degrading enzymes in bacteria. Here, Izquierdo-Martinez et al. show that one such protein, DipM, coordinates different peptidoglycan-remodeling pathways to ensure proper cell constriction and daughter cell separation in the model bacterium Caulobacter crescentus.
- Adrian Izquierdo-Martinez
- , Maria Billini
- & Martin Thanbichler
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Article
| Open AccessAn RNA modification enzyme directly senses reactive oxygen species for translational regulation in Enterococcus faecalis
Here the authors found an RNA modifying enzyme that serves as a molecular switch, directly relaying the sensing of reactive oxygen species to chemical modifications in rRNA and tRNA for increasing stress response proteins in the proteome.
- Wei Lin Lee
- , Ameya Sinha
- & Peter Dedon
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Article
| Open AccessRoving methyltransferases generate a mosaic epigenetic landscape and influence evolution in Bacteroides fragilis group
Here, Tisza, Dekker, and colleagues perform large scale analysis of genome methylation in the gut commensal and pathogen, Bacteroides fragilis group, revealing immense methyl motif diversity and evidence of widespread methyltransferase exchange among phages.
- Michael J. Tisza
- , Derek D. N. Smith
- & John P. Dekker
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Article
| Open AccessMolecular basis and design principles of switchable front-rear polarity and directional migration in Myxococcus xanthus
Cell polarity is key to many processes in bacteria. By focusing on the roadblock domain protein MglC, the authors elucidate the mechanistic basis and design principles of a system that spatiotemporally regulates switchable front-rear polarity and directional migration.
- Luís António Menezes Carreira
- , Dobromir Szadkowski
- & Lotte Søgaard-Andersen
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Article
| Open AccessMolecular mechanism of plasmid-borne resistance to sulfonamide antibiotics
Bacterial resistance to sulfonamide antibiotics (sulfas) is mediated by acquisition of sul genes, which encode sulfa-insensitive versions of the target enzyme, dihydropteroate synthase. Here, Venkatesan et al. study Sul enzymes using biochemical, structural, mutational and functional analyses, revealing the molecular basis for Sul-mediated drug resistance.
- Meenakshi Venkatesan
- , Michael Fruci
- & Alexei Savchenko
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Article
| Open AccessMembrane translocation process revealed by in situ structures of type II secretion system secretins
In this work the authors investigate two types of secretins in Escherichia coli, GspDα and GspDβ, and report the Cryo-ET in situ structures of their key intermediate states of during the translocation process. Yielding a resolution ranging from 9 Å to 19 Å, the structures allow the identification of different membrane interaction patterns and ways of transitioning the peptidoglycan layer. These results suggest two distinct models for the membrane translocation of GspDα and GspDβ and provide insights into the inner to outer membrane biogenesis of T2SS secretins.
- Zhili Yu
- , Yaoming Wu
- & Zhao Wang
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Article
| Open AccessExtensive diversity in RNA termination and regulation revealed by transcriptome mapping for the Lyme pathogen Borrelia burgdorferi
Transcription termination can tune bacterial gene expression in response to diverse signals. Here, the authors use several RNA-seq approaches to map RNA ends for the transcriptome of the spirochete Borrelia burgdorferi, providing insights into various modes of transcription termination and identifying potential RNA regulators in this pathogen.
- Emily Petroni
- , Caroline Esnault
- & Philip P. Adams
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Article
| Open AccessDprE2 is a molecular target of the anti-tubercular nitroimidazole compounds pretomanid and delamanid
Pretomanid and delamanid are pro-drugs used for the treatment of tuberculosis, but their precise mechanisms of action are unclear. Here, the authors identify an enzyme required for the synthesis of the mycobacterial cell wall as a molecular target of the activated drugs.
- Katherine A. Abrahams
- , Sarah M. Batt
- & Gurdyal S. Besra
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Article
| Open AccessNOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice
Maturation of interleukin-18 (IL-18) is normally mediated by activated inflammasomes in innate immune cells as an antipathogen mechanism. Here the authors show that IL-18 maturation occurs in gut epithelial cells upon encounter with Helicobacter pylorivia a noncanonical NOD1/caspase-1 pathway to maintain epithelial homoeostasis.
- L. S. Tran
- , L. Ying
- & R. L. Ferrero
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Article
| Open AccessGenomic epidemiology of Vibrio cholerae during a mass vaccination campaign of displaced communities in Bangladesh
The Cox’s Bazar area of Bangladesh has received a large number of Forcibly Displaced Myanmar Nationals. Cholera outbreaks have been detected in the area, and here, the authors perform genomic surveillance of cholera in the refugee and non-refugee population to infer the risk of epidemic spread.
- Alyce Taylor-Brown
- , Mokibul Hassan Afrad
- & Firdausi Qadri
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Article
| Open AccessEpistatic interactions between the high pathogenicity island and other iron uptake systems shape Escherichia coli extra-intestinal virulence
The virulence of extra-intestinal pathogenic Escherichia coli is associated with multiple different genes in different lineages. Here, Royer et al. show that the emergence of virulence is associated with acquisition of the siderophore-encoding high-pathogenicity island (HPI), and full virulence is associated with the additional presence of the aer or sit operons.
- Guilhem Royer
- , Olivier Clermont
- & Erick Denamur
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Article
| Open AccessEvolutionary and functional history of the Escherichia coli K1 capsule
Little is known about the distribution, evolution and functions of the K1 capsule at a population level, despite the important role in the pathogenesis of E. coli; authors explore this through the utilisation of over 5,000 clinical isolates in population genomics studies and statistical modelling.
- Sergio Arredondo-Alonso
- , George Blundell-Hunter
- & Alex J. McCarthy
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Article
| Open AccessAllosteric activation of cell wall synthesis during bacterial growth
Coordination of cell wall assembly is critical for bacterial morphology and survival. Here, the authors show that activation of cell wall synthesis by the Rod complex is regulated by the structural dynamics of RodA-PBP2.
- Irina Shlosman
- , Elayne M. Fivenson
- & Joseph J. Loparo
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Article
| Open AccessQuorum sensing as a mechanism to harness the wisdom of the crowds
Bacteria release and respond to autoinducers in a process known as quorum sensing. While classically viewed as a strategy to coordinate cell behaviour, Moreno-Gámez et al. demonstrate using modelling that quorum sensing may also be used to sense the environment as a collective by pooling information at relevant scales and harnessing the wisdom of the crowds.
- Stefany Moreno-Gámez
- , Michael E. Hochberg
- & G. S. van Doorn
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Article
| Open AccessEfflux pump gene amplifications bypass necessity of multiple target mutations for resistance against dual-targeting antibiotic
Antibiotics that attack multiple targets in bacteria are thought to reduce the frequency of resistance. The authors show that genomic amplifications of poorly characterized efflux pumps can instead lead to high-frequency antibiotic cross-resistance.
- Kalinga Pavan T. Silva
- , Ganesh Sundar
- & Anupama Khare
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Article
| Open AccessMultiple ParA/MinD ATPases coordinate the positioning of disparate cargos in a bacterial cell
The ParA/MinD family of ATPases organize diverse genetic- and protein-based cellular cargos in bacteria. Here, Pulianmackal et al. find that over a third of sequenced bacterial genomes encode multiple ParA/MinD ATPases, and show how multiple ParA/MinD ATPases coexist and function to position diverse cargos in the same bacterial cell.
- Lisa T. Pulianmackal
- , Jose Miguel I. Limcaoco
- & Anthony G. Vecchiarelli
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Article
| Open AccessBacteriophage targeting microbiota alleviates non-alcoholic fatty liver disease induced by high alcohol-producing Klebsiella pneumoniae
Previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Here, the authors show the effectiveness of phage in mice with HiAlc Kpn-induced NAFLD indicating phage therapy targeting gut microbiota may be an alternative to antibiotics, with potential efficacy and safety.
- Lin Gan
- , Yanling Feng
- & Jing Yuan
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Article
| Open AccessStress-induced metabolic exchanges between complementary bacterial types underly a dynamic mechanism of inter-species stress resistance
Microbes can cooperate and share resources via metabolic cross-feeding. Here, the authors show that excretion of key metabolites following acid stress provides a collaborative, inter-species mechanism of stress resistance.
- Kapil Amarnath
- , Avaneesh V. Narla
- & Terence Hwa
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Article
| Open AccessSimultaneous sulfide and methane oxidation by an extremophile
Aerobic methanotrophic bacteria oxidize methane in sulfide-rich environments, even though hydrogen sulfide (H2S) inhibits methane oxidation and aerobic respiration. Here, Schmitz et al. show that a single microorganism can oxidize methane and H2S simultaneously, and this is associated with upregulation of a sulfide-insensitive terminal oxidase.
- Rob A. Schmitz
- , Stijn H. Peeters
- & Arjan Pol
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Article
| Open AccessDe novo cholesterol biosynthesis in bacteria
Production of highly modified sterols, such as cholesterol, is essential to eukaryotic physiology but has not been yet reported for bacteria. Here, Lee et al. show that a marine myxobacterium produces cholesterol, and provide evidence for further downstream modifications in this and other bacterial species.
- Alysha K. Lee
- , Jeremy H. Wei
- & Paula V. Welander
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Article
| Open AccessSelenomonas sputigena acts as a pathobiont mediating spatial structure and biofilm virulence in early childhood caries
Streptococcus mutans (S. mutans) has been implicated as a major pathogen in childhood caries. Here, the authors show that Selenomonas sputigena, a flagellated anaerobe, interacts with S. mutans in the supragingival biofilm, builds a honeycomb-like multicellular-superstructure that encapsulates it, and promotes the development of childhood dental caries.
- Hunyong Cho
- , Zhi Ren
- & Hyun Koo
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Article
| Open AccessStructural analysis and architectural principles of the bacterial amyloid curli
Using Alpha fold modelling and cryo-EM reconstruction the authors reveal the structural and architectural principles of the bacterial functional amyloid curli, encompassing the continuous stacking of β-solenoid pseudo repeats within and across subunits.
- Mike Sleutel
- , Brajabandhu Pradhan
- & Han Remaut
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Article
| Open AccessRoles of adenine methylation in the physiology of Lacticaseibacillus paracasei
The bacterium Lacticaseibacillus paracasei is used in the food industry and as a probiotic. Here, the authors use multi-omics and high-throughput chromosome conformation capture analyses to investigate the roles of a type of DNA methylation (N6-methyladenine modification) in this organism.
- Jie Zhao
- , Meng Zhang
- & Wenyi Zhang
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Article
| Open AccessPulcherriminic acid modulates iron availability and protects against oxidative stress during microbial interactions
Microbes often produce molecules (termed siderophores) that bind iron and then are taken up using specific receptors for iron acquisition. Here, the authors show that a compound produced by Bacillus subtilis plays a more complex role, by modulating iron availability and conferring protection against oxidative stress during inter-species competition.
- Vincent Charron-Lamoureux
- , Lounès Haroune
- & Pascale B. Beauregard
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Article
| Open AccessA link between STK signalling and capsular polysaccharide synthesis in Streptococcus suis
Serine/threonine kinases (STKs) regulate the synthesis of capsular polysaccharide in bacteria through unclear mechanisms. Here, Tang et al. identify a protein that is phosphorylated by an STK and modulates the activity of a phosphoregulatory system in Streptococcus suis, thus linking STKs to capsular polysaccharide synthesis.
- Jinsheng Tang
- , Mengru Guo
- & Hongjie Fan
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Article
| Open AccessStructural basis for botulinum neurotoxin E recognition of synaptic vesicle protein 2
Botulinum neurotoxin E (BoNT/E) is a major cause of botulism and paradoxically also a drug in clinical trial. Here, the authors show that BoNT/E binding and uptake require glycosylation of its host receptor SV2 with high selectivity for SV2A and SV2B over SV2C.
- Zheng Liu
- , Pyung-Gang Lee
- & Rongsheng Jin
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Article
| Open AccessIn vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter
Bioluminescent imaging of bacteria in vivo generally requires the use of engineered bacteria. Here the authors take advantage of bacteria specific ATP-binding cassette sugar transporters to enable selective delivery of bioluminescent nanoprobes into bacteria for visualisation, including in deep tissues.
- Qian Zhang
- , Bin Song
- & Yao He
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Article
| Open AccessStructural insights into RNase J that plays an essential role in Mycobacterium tuberculosis RNA metabolism
Here the authors report the crystal structures of RNase J from Mycobacterium tuberculosis in apo-state and complex with single strand RNA, revealing its physiological function in RNA metabolism.
- Luyao Bao
- , Juan Hu
- & Jixi Li
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Article
| Open AccessHuman CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
Infection with Streptococcus pyogenes after childbirth can have life threatening consequences. Here, Catton et al. show that the epidemiologically associated bacterial R28 protein targets the human CEACAM1 receptor to facilitate the pathogenesis of bacterial sepsis.
- Erin A. Catton
- , Daniel A. Bonsor
- & Alex J. McCarthy
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Article
| Open AccessDephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b
During infection, the Legionella effector Lem3 removes a phosphocholine moiety from the human protein Rab1. Here, the authors present the crystal structure of the stabilised Lem3:Rab1b complex, revealing the catalytic mechanism and substrate recognition of PPM phosphatases shaped Lem3.
- Marietta S. Kaspers
- , Vivian Pogenberg
- & Aymelt Itzen
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Article
| Open AccessIdentification of d-arabinan-degrading enzymes in mycobacteria
Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, the authors identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria.
- Omar Al-Jourani
- , Samuel T. Benedict
- & Patrick J. Moynihan
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