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| Open AccessNascent RNA sequencing identifies a widespread sigma70-dependent pausing regulated by Gre factors in bacteria
Transcription by bacterial RNA polymerase is interrupted by pausing events that play diverse regulatory roles. Here, the authors find that a large number of E. coli sigma70-dependent pauses, clustered at a 10−20-bp distance from promoters, are regulated by Gre cleavage factors constituting a mechanism for rapid response to changing environmental cues.
- Zhe Sun
- , Alexander V. Yakhnin
- & Mikhail Kashlev
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| Open AccessCultivation of elusive microbes unearthed exciting biology
Many newly-discovered microbial phyla have been studied solely by cultivation-independent techniques such as metagenomics. Much of their biology thus remains elusive, because the organisms have not yet been isolated and grown in the lab. Katayama et al. lift the curtain on some intriguing biology by cultivating and studying bacteria from the elusive OP9 phylum (Atribacterota).
- Muriel C. F. van Teeseling
- & Christian Jogler
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Article
| Open AccessInsights into SusCD-mediated glycan import by a prominent gut symbiont
In Bacteroidetes, SusCD complexes mediate uptake of large nutrients across the outer membrane. SusCD structures in the apo state and in complex with β2,6 fructo-oligosaccharides reveal several substrate molecules in the binding cavity and suggest details of the pedal bin mechanism employed in glycan import.
- Declan A. Gray
- , Joshua B. R. White
- & Bert van den Berg
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Article
| Open AccessThe iron-dependent repressor YtgR is a tryptophan-dependent attenuator of the trpRBA operon in Chlamydia trachomatis
Chlamydia trachomatis does not possess TrpL-mediated transcription attenuation of its trp operon. Here, the authors show that an iron-dependent regulator, YtgR, acts as a tryptophan-dependent attenuator of the trp operon in this organism, due to translational regulation of YtgR levels via a triple tryptophan motif.
- Nick D. Pokorzynski
- , Nathan D. Hatch
- & Rey A. Carabeo
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Article
| Open AccessReceptor-targeted engineered probiotics mitigate lethal Listeria infection
Here, the authors characterize the effects of Lactobacillus casei strains engineered to express pathogenic or non-pathogenic Listeria adhesion protein (LAP) in systemic colonization and protection against lethal Listeria monocytogenes infection in mice and show that these engineered strains can colonize the intestine and prevent dissemination of L. monocytogenes and protect against lethal infection while promoting immunomodulatory effects.
- Rishi Drolia
- , Mary Anne Roshni Amalaradjou
- & Arun K. Bhunia
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Article
| Open AccessConstruction of a complete set of Neisseria meningitidis mutants and its use for the phenotypic profiling of this human pathogen
The bacterium Neisseria meningitidis causes life-threatening meningitis and sepsis. Here, Muir et al. construct a complete collection of defined mutants in protein-coding genes of this organism, which they use to identify its essential genome and to shed light on the functions of multiple genes.
- Alastair Muir
- , Ishwori Gurung
- & Vladimir Pelicic
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| Open AccessProphage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes
The pathogenesis of Streptococcus pyogenes (GAS) causing scarlet fever has been associated with the presence of prophages, such as ΦHKU.vir, and their products. Here, the authors characterize the exotoxins SpeC and Spd1 of ΦHKU.vir and show these to act synergistically to facilitate nasopharyngeal colonization in mice.
- Stephan Brouwer
- , Timothy C. Barnett
- & Mark J. Walker
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Article
| Open AccessGenomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae
Pandemic cholera was reintroduced to Argentina in 1992, leading to epidemic spread. Here, the authors use whole genome sequencing to show how, over 6 years, epidemic cholera was caused by invariant 7PET lineage Vibrio cholerae, against a background of sporadic disease caused by diverse local strains.
- Matthew J. Dorman
- , Daryl Domman
- & Nicholas R. Thomson
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Article
| Open AccessMammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization
Histones have a role in antimicrobial defense. Here, the authors show that the histone H2A and the antimicrobial peptide LL-37 exert synergistic effects by enhancing bacterial membrane pores and enabling H2A entry into the bacterial cytoplasm, where it reorganizes DNA and inhibits transcription.
- Tory Doolin
- , Henry M. Amir
- & Albert Siryaporn
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Article
| Open AccessBreast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression
High levels of Fusobacterium nucleatum have been associated with poor overall survival in patients with colorectal and esophageal cancer. Here, the authors show that F. nucleatum is abundant in breast cancer samples and that the colonization by F. nucleatum accelerates tumor growth and metastasis in preclinical breast cancer models.
- Lishay Parhi
- , Tamar Alon-Maimon
- & Gilad Bachrach
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Article
| Open AccessMechanism of effector capture and delivery by the type IV secretion system from Legionella pneumophila
A membrane-embedded complex (called T4CC) is essential for injection of Legionella pneumophila effector proteins into human macrophages via a Type IV secretion system. Here, the authors purify and study the T4CC using functional and cryo-EM structural analyses, providing insights into the secretion mechanisms.
- Amit Meir
- , Kevin Macé
- & Gabriel Waksman
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Article
| Open AccessThe phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia
Multidrug resistance of the opportunistic pathogen Stenotrophomonas maltophilia is an increasing problem. Here, analyzing strains from 22 countries, the authors show that the S. maltophilia complex is divided into 23 monophyletic lineages and find evidence for intra-hospital transmission.
- Matthias I. Gröschel
- , Conor J. Meehan
- & Thomas A. Kohl
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Article
| Open AccessDonor-delivered cell wall hydrolases facilitate nanotube penetration into recipient bacteria
Bacteria can produce membranous nanotubes that mediate contact-dependent exchange of molecules between bacterial cells. Here, Baidya et al. show that cell-wall remodelling enzymes from Bacillus subtilis are required for efficient nanotube extrusion and penetration, and can be delivered to other bacterial species via nanotubes.
- Amit K. Baidya
- , Ilan Rosenshine
- & Sigal Ben-Yehuda
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Article
| Open AccessIncreased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin
The mechanisms behind the high invasiveness of Streptococcus pneumoniae serotype 1 are unclear. Here, Jacques et al. show that this feature is due to overproduction and rapid release of pneumolysin, which induces cytotoxicity and breakdown of tight junctions, allowing rapid bacterial dissemination from the respiratory tract into the blood.
- Laura C. Jacques
- , Stavros Panagiotou
- & Aras Kadioglu
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Article
| Open AccessGlycolytic reprograming in Salmonella counters NOX2-mediated dissipation of ΔpH
Chakraborty et al. show that phagocyte NADPH oxidase (NOX2) collapses the ΔpH of intracellular Salmonella Typhimurium, leading to oxidative damage of cell envelope proteins. Salmonella responds by shifting redox balance from respiration to glycolysis and fermentation, thereby facilitating folding of periplasmic functions.
- Sangeeta Chakraborty
- , Lin Liu
- & Andres Vazquez-Torres
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Article
| Open AccessLipoprotein Lpp regulates the mechanical properties of the E. coli cell envelope
Lipoprotein Lpp provides a covalent crosslink between the outer membrane and the peptidoglycan in E. coli. Here, the authors use atomic force microscopy to show that Lpp contributes to cell envelope stiffness by covalently connecting the two layers and by controlling the width of the periplasmic space.
- Marion Mathelié-Guinlet
- , Abir T. Asmar
- & Yves F. Dufrêne
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Article
| Open AccessSingle-molecule live-cell imaging visualizes parallel pathways of prokaryotic nucleotide excision repair
In Escherichia coli, the UvrAB damage sensor recognizes helix-distorting lesions by itself or via Mfd bound to stalled RNA polymerase. Here authors use single-molecule fluorescence imaging to quantify the kinetic signatures of interactions of UvrA with Mfd and UvrB in live cells.
- Harshad Ghodke
- , Han Ngoc Ho
- & Antoine M. van Oijen
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Article
| Open AccessSingle-molecule imaging reveals molecular coupling between transcription and DNA repair machinery in live cells
Mfd recognizes stalled transcriptional complexes at sites of lesions and recruits the nucleotide excision repair proteins (UvrAB) to the site. Here the authors use live cell imaging in E. coli to demonstrate that coordinated ATP hydrolysis by UvrA and loading of UvrB on DNA facilitate the dissociation of Mfd from the handoff complex.
- Han Ngoc Ho
- , Antoine M. van Oijen
- & Harshad Ghodke
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Article
| Open AccessA comparative genomics methodology reveals a widespread family of membrane-disrupting T6SS effectors
Gram-negative bacteria deliver effectors via the type VI secretion system (T6SS) to outcompete their rivals. Here, Fridman et al. present an approach to identify T6SS effectors encoded in bacterial genomes without prior knowledge of their domain content or genetic neighbourhood, and identify a new family of membrane-disrupting effectors.
- Chaya M. Fridman
- , Kinga Keppel
- & Dor Salomon
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Article
| Open AccessPrecise timing of transcription by c-di-GMP coordinates cell cycle and morphogenesis in Caulobacter
Bacteria adapt their growth rate to their metabolic status and environmental conditions by modulating the length of their G1 period. Here the authors show that an increase in c-di-GMP concentration modulates the activity of kinase ShkA and transcription factor TacA, thus enabling G1/S transition in Caulobacter.
- Andreas Kaczmarczyk
- , Antje M. Hempel
- & Urs Jenal
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Article
| Open AccessSystemic infection facilitates transmission of Pseudomonas aeruginosa in mice
Pseudomonas aeruginosa bacteremia is presumed to be a ‘dead-end’ for the pathogen and to have no impact on transmission. Here the authors show, in mice, that the bacteria can spread from the bloodstream via the gallbladder to the intestines and feces, leading to transmission to uninfected animals.
- Kelly E. R. Bachta
- , Jonathan P. Allen
- & Alan R. Hauser
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Article
| Open AccessInhibiting bacterial cooperation is an evolutionarily robust anti-biofilm strategy
Bacterial biofilms rely on shared extracellular polymeric substances (EPS) and are often highly tolerant to antibiotics. Here, the authors show in in vitro experiments that Salmonella does not evolve resistance to EPS inhibition because such strains are outcompeted by a susceptible strain under inhibitor treatment.
- Lise Dieltjens
- , Kenny Appermans
- & Hans P. Steenackers
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Article
| Open AccessYtfK activates the stringent response by triggering the alarmone synthetase SpoT in Escherichia coli
The enzyme SpoT is important for accumulation of the alarmone (p)ppGpp, which triggers the stringent response in E. coli. Here, Germain et al. show that the protein YtfK promotes SpoT-dependent accumulation of (p)ppGpp and is required for activation of the stringent response during phosphate and fatty acid starvation.
- Elsa Germain
- , Paul Guiraud
- & Etienne Maisonneuve
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Article
| Open AccessA family of Type VI secretion system effector proteins that form ion-selective pores
Type VI secretion systems (T6SSs) are used by bacteria to inject toxic effector proteins into neighbouring cells. Here, Mariano et al. show that an antibacterial effector from Serratia marcescens forms cation-selective pores that lead to inner-membrane depolarisation and increased outer-membrane permeability.
- Giuseppina Mariano
- , Katharina Trunk
- & Sarah J. Coulthurst
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Article
| Open AccessCore architecture of a bacterial type II secretion system
Bacterial type II secretion systems (T2SSs) translocate virulence factors, toxins and enzymes across the cell outer membrane. Here, Chernyatina and Low use negative stain and cryo-electron microscopy to reveal the core architecture of an assembled T2SS from the pathogen Klebsiella pneumoniae.
- Anastasia A. Chernyatina
- & Harry H. Low
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Article
| Open AccessIdentification of the periplasmic DNA receptor for natural transformation of Helicobacter pylori
Some bacteria can take up DNA molecules from the environment. Here, Damke et al. identify a DNA-binding protein in Helicobacter pylori that is required for DNA import into the periplasm and that interacts with an inner-membrane channel that translocates the DNA into the cytoplasm.
- Prashant P. Damke
- , Anne Marie Di Guilmi
- & J. Pablo Radicella
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Article
| Open AccessConditional quorum-sensing induction of a cyanide-insensitive terminal oxidase stabilizes cooperating populations of Pseudomonas aeruginosa
Quorum sensing (QS) regulates production of ‘public goods’ by Pseudomonas aeruginosa, which releases toxic hydrogen cyanide to constrain QS-deficient cheaters. Here, Yan et al. show that QS-proficient strains protect themselves by producing a cyanide-insensitive enzyme in response to reactive oxygen species released by cheaters.
- Huicong Yan
- , Kyle L. Asfahl
- & Meizhen Wang
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Article
| Open AccessEfficient inter-species conjugative transfer of a CRISPR nuclease for targeted bacterial killing
CRISPR nucleases can be programmed to cleave sequences in specific bacteria to induce cell death. Here, Hamilton et al. present an optimized method for conjugative delivery of CRISPR nucleases, consisting of a single plasmid that encodes both the conjugative machinery and the nuclease.
- Thomas A. Hamilton
- , Gregory M. Pellegrino
- & David R. Edgell
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Article
| Open AccessIntegrated evolutionary analysis reveals antimicrobial peptides with limited resistance
Antimicrobial peptides (AMPs) are emerging as drug candidates, but the risk of pathogen resistance is not well understood. Here, the authors investigate AMP resistance evolution in E. coli, finding physicochemical features that make AMPs less prone to resistance and no cross- or horizontally-acquired resistance.
- Réka Spohn
- , Lejla Daruka
- & Csaba Pál
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Article
| Open AccessDerailing the aspartate pathway of Mycobacterium tuberculosis to eradicate persistent infection
Amino acid biosynthetic pathways are an attractive alternative to treat chronic infections such as Mycobacterium tuberculosis (Mtb). Here, the authors investigate the metabolic response to disruption of the aspartate pathway in persistent Mtb and identify essential enzymes as potential new targets for drug development.
- Erik J. Hasenoehrl
- , Dannah Rae Sajorda
- & Michael Berney
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Article
| Open AccessAlternate subunit assembly diversifies the function of a bacterial toxin
Salmonella Typhi produces the typhoid toxin. Here, Fowler et al. show that S. Typhi produces two forms of typhoid toxin that are differentially regulated and display different trafficking properties and different effects when administered to laboratory animals.
- Casey C. Fowler
- , Gabrielle Stack
- & Jorge E. Galán
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Article
| Open AccessMpsAB is important for Staphylococcus aureus virulence and growth at atmospheric CO2 levels
The mechanisms behind CO2 dependency in non-autotrophic bacterial isolates are unclear. Here the authors show that the Staphylococcus aureus mpsAB operon is crucial for growth at atmospheric CO2 levels, and provide evidence indicating that MpsAB represents a bicarbonate concentrating system.
- Sook-Ha Fan
- , Patrick Ebner
- & Friedrich Götz
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Article
| Open AccessA modular effector with a DNase domain and a marker for T6SS substrates
Bacteria deliver toxic effectors via type VI secretion systems (T6SSs) to dominate competitors. Here, the authors identify a Vibrio antibacterial effector that contains a new DNase toxin domain and a domain of unknown function that can be used as a marker to identify new T6SS effectors.
- Biswanath Jana
- , Chaya M. Fridman
- & Dor Salomon
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Article
| Open AccessThe Salmonella virulence protein MgtC promotes phosphate uptake inside macrophages
The virulence factor MgtC is essential for intracellular macrophage survival of Salmonella enterica. Here, the authors show that MgtC targets the PhoB/PhoR regulatory system leading to phosphate uptake inside macrophages and that both phoR mutation and phoB deletion renders Salmonella hypervirulent in mice.
- Soomin Choi
- , Eunna Choi
- & Eun-Jin Lee
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Article
| Open AccessTransient drug-tolerance and permanent drug-resistance rely on the trehalose-catalytic shift in Mycobacterium tuberculosis
Trehalose metabolism has been linked to Mycobacterium tuberculosis (Mtb) virulence and biofilm formation. Here, using a model of drug-tolerant persisters and metabolomics, the authors dissect the role of trehalose metabolism in Mtb persister formation, linking trehalose-catalytic shift to antibiotic resistance.
- Jae Jin Lee
- , Sun-Kyung Lee
- & Hyungjin Eoh
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Article
| Open AccessRadical-mediated C-S bond cleavage in C2 sulfonate degradation by anaerobic bacteria
The C2 sulfonates taurine and isethionate are also present in the anaerobic mammalian gut, where they are converted into toxic H2S by sulfate and sulfite-reducing bacteria. Here the authors characterise the O2-sensitive enzyme IseG that catalyzes the C-S bond cleavage of isethionate and show that IseG also plays a key role in converting taurine into H2S in Bilophila wadsworthia.
- Meining Xing
- , Yifeng Wei
- & Yan Zhang
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Article
| Open AccessExtreme slow growth as alternative strategy to survive deep starvation in bacteria
Bacteria can become dormant or form spores when starved for nutrients. Here, Gray et al. describe an alternative strategy, or ‘oligotrophic growth state’, showing that non-sporulating Bacillus subtilis cells can survive deep starvation conditions by adopting an almost coccoid shape and extremely low growth rates.
- Declan A. Gray
- , Gaurav Dugar
- & Leendert W. Hamoen
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Article
| Open AccessStress-induced inactivation of the Staphylococcus aureus purine biosynthesis repressor leads to hypervirulence
PurR acts as transcriptional repressor of purine biosynthesis genes in some bacterial species. Here, the authors show that purR mutations can arise in Staphylococcus aureus upon exposure to stress, leading to upregulation of fibronectin-binding proteins and increased virulence.
- Mariya I. Goncheva
- , Ronald S. Flannagan
- & David E. Heinrichs
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Article
| Open AccessAn electrogenic redox loop in sulfate reduction reveals a likely widespread mechanism of energy conservation
The bacterial complex QrcABCD plays a key role in the bioenergetics of sulfate respiration. Here, Duarte et al. show that this complex is electrogenic, with protons and electrons required for quinone reduction being extracted from opposite sides of the membrane.
- Américo G. Duarte
- , Teresa Catarino
- & Inês A. C. Pereira
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Article
| Open AccessEscherichia coli can survive stress by noisy growth modulation
Noisy gene expression leading to phenotypic variability can help organisms to survive in changing environments. Here, Patange et al. show that noisy expression of a stress response regulator, RpoS, allows E. coli cells to modulate their growth rates to survive future adverse environments.
- Om Patange
- , Christian Schwall
- & James C. W. Locke
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Article
| Open AccessZ-ring membrane anchors associate with cell wall synthases to initiate bacterial cell division
Proteins FtsZ, ZipA, and either PBP1A or PBP1B are required for the synthesis of preseptal peptidoglycan at the future cell division site in E. coli. Here, Pazos et al. provide evidence that ZipA and FtsA-FtsN connect the cytosolic FtsZ ring with the membrane-anchored PBPs.
- Manuel Pazos
- , Katharina Peters
- & Waldemar Vollmer
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Article
| Open AccessHydrogen production by Sulfurospirillum species enables syntrophic interactions of Epsilonproteobacteria
Epsilonproteobacteria, such as Sulfurospirillum, can use molecular hydrogen as an electron donor for respiration. Here, the authors show that Sulfurospirillum can, in addition, release hydrogen during fermentation, allowing metabolic interactions with other hydrogen-consuming microorganisms.
- Stefan Kruse
- , Tobias Goris
- & Gabriele Diekert
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Article
| Open AccessMicroevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection
Carriage of Neisseria lactamica, a harmless coloniser of the human respiratory tract, is inversely correlated with Neisseria meningitidis infection. Here, Pandey et al. provide insights into micro-evolutionary processes in N. lactamica during controlled infection of healthy volunteers.
- Anish Pandey
- , David W. Cleary
- & Robert C. Read
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Article
| Open AccessHost suppression of quorum sensing during catheter-associated urinary tract infections
Pseudomonas aeruginosa can cause chronic infections on medical devices by forming biofilms, a process regulated by quorum sensing (QS). Here, the authors show that P. aeruginosa is unable to perceive QS signals in the presence of either host urine or urea, and clinical isolates are often defective in QS.
- Stephanie J. Cole
- , Cherisse L. Hall
- & Vincent T. Lee
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Article
| Open AccessCell shape-independent FtsZ dynamics in synthetically remodeled bacterial cells
The FtsZ protein assembles into a structure known as ‘Z-ring’ at midcell for bacterial cell division. Here, Söderström et al. show that Z-ring assembly and dynamics in E. coli cells with unnatural shapes, such as squares and hearts, are generally similar to those observed in cells with normal shape.
- Bill Söderström
- , Alexander Badrutdinov
- & Ulf Skoglund
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Article
| Open AccessHost-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion
Infection of mice with Citrobacter rodentium is a common model of infection with attaching-and-effacing pathogens. Here, Connolly et al. analyse the transcriptome of C. rodentium during mouse infection, showing host-induced coordinated upregulation of virulence factors and 1,2-propanediol metabolism.
- James P. R. Connolly
- , Sabrina L. Slater
- & Andrew J. Roe
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Article
| Open AccessProlonged bacterial lag time results in small colony variants that represent a sub-population of persisters
Persisters are bacterial subpopulations that are not killed by antibiotics even though they lack genetic resistance. Here, the authors show that persisters can manifest as small colony variants in clinical infections, and arise as a result of a long lag time in stress conditions including antibiotic exposure.
- Clément Vulin
- , Nadja Leimer
- & Annelies S. Zinkernagel
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Article
| Open Access"RETRACTED ARTICLE: Vibrio parahaemolyticus RhsP represents a widespread group of pro-effectors for type VI secretion systems
It is unclear how Rhs toxins lacking a PAAR motif are secreted by Type VI secretion systems. Here, the authors show for one of these proteins that the mechanism requires removal of an N-terminal fragment by auto-proteolysis, followed by interaction with a PAAR protein and then secretion.
- Nan Jiang
- , Le Tang
- & Jun Zheng
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Article
| Open AccessConserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli
Resistance to one antibiotic can in some cases increase susceptibility to other antibiotics. Here, Podnecky et al. study these collateral responses in E. coli clinical isolates and show that efflux-related resistance mechanisms and relative fitness of the strains are principal contributors to this phenomenon.
- Nicole L. Podnecky
- , Elizabeth G. A. Fredheim
- & Pål J. Johnsen