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| Open AccessHorizontally acquired papGII-containing pathogenicity islands underlie the emergence of invasive uropathogenic Escherichia coli lineages
Escherichia coli is a major cause of urinary tract infection. Here, Biggel et al. provide a phylogenomic analysis of 907 clinical E. coli isolates and identify the P-fimbriae-encoding locus associated with invasive uropathogenic E. coli isolates.
- Michael Biggel
- , Basil B. Xavier
- & Sandra Van Puyvelde
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Article
| Open AccessHigh-throughput laboratory evolution reveals evolutionary constraints in Escherichia coli
Understanding evolutionary constraints in antibiotic resistance is crucial for prediction and control. Here, the authors use high-throughput laboratory evolution of Escherichia coli alongside machine learning to identify trade-off relationships associated with drug resistance.
- Tomoya Maeda
- , Junichiro Iwasawa
- & Chikara Furusawa
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Article
| Open AccessPiperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B
An E. coli and K. pneumoniae phenotype resistant to piperacillin/tazobactam has recently emerged. Here, the authors show that hyperproduction of the β-lactamase driving this resistance occurs due to excision and reinsertion of a translocatable unit containing blaTEM-1B, creating a tandem array.
- Alasdair T. M. Hubbard
- , Jenifer Mason
- & Thomas Edwards
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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 AccessEfflux pump activity potentiates the evolution of antibiotic resistance across S. aureus isolates
Some bacterial lineages appear to be pre-disposed to evolving antibiotic resistance. Here, the authors show that differential expression of an efflux pump causes widespread variation in evolvability across Staphylococcus aureus isolates, and chemical inhibition of the pump prevents resistance evolution.
- Andrei Papkou
- , Jessica Hedge
- & R. Craig MacLean
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Article
| Open AccessPathways for horizontal gene transfer in bacteria revealed by a global map of their plasmids
Plasmids can mediate gene transfer across bacterial populations. Here, the authors describe a global map of the prokaryotic plasmidome, where plasmids organize into discrete ‘plasmid taxonomic units’ based on their genomic composition and pairwise sequence identity.
- Santiago Redondo-Salvo
- , Raúl Fernández-López
- & Fernando de la Cruz
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Article
| Open AccessWithin-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation
Streptococcus pneumoniae is an opportunistic pathogen and asymptomatic colonization is a precursor for invasive disease. Here the authors show rapid within-host evolution of naturally acquired pneumococci in ninety-eight infants driven by high nucleotide substitution rates and intra-host homologous recombination.
- Chrispin Chaguza
- , Madikay Senghore
- & Brenda A. Kwambana-Adams
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| Open AccessPrecise phylogenetic analysis of microbial isolates and genomes from metagenomes using PhyloPhlAn 3.0
The increasing amount of sequenced microbial genomes and metagenomes requires platforms for efficient integrated analysis. Here, Asnicar et al. present PhyloPhlAn 3.0, a pipeline allowing large-scale microbial genome characterization and phylogenetic contextualization at multiple levels of resolution.
- Francesco Asnicar
- , Andrew Maltez Thomas
- & Nicola Segata
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| Open AccessThe route to transcription initiation determines the mode of transcriptional bursting in E. coli
Transcription noise in bacteria is often attributed to burstiness, but the mechanisms are unclear. Here, the authors show that the transition from low to high expression can be regulated via burst size or burst frequency, depending on the mode of transcription initiation determined by different sigma factors.
- Christoph Engl
- , Goran Jovanovic
- & Martin Buck
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Article
| Open AccessThe circadian clock and darkness control natural competence in cyanobacteria
The cyanobacterium Synechococcus elongatus is a model organism for the study of circadian rhythms, and is naturally competent for transformation. Here, Taton et al. identify genes required for natural transformation in this organism, and show that the coincidence of circadian dusk and darkness regulates the competence state in different day lengths.
- Arnaud Taton
- , Christian Erikson
- & Susan S. Golden
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| Open AccessAn acid-tolerance response system protecting exponentially growing Escherichia coli
The ability to grow at acidic pH is crucial for E. coli colonization of the host’s intestine. Here, the authors identify an acid-tolerance response system that is important for E. coli exponential growth at pH 4.2, survival in the mouse intestine, and production of 3-hydroxypropionate during fermentation.
- Ying Xu
- , Zhe Zhao
- & Guang Zhao
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Article
| Open AccessDominant resistance and negative epistasis can limit the co-selection of de novo resistance mutations and antibiotic resistance genes
The authors study the interactions between chromosomal mutations and horizontally acquired genes in the evolution of antibiotic resistance in experimental evolution assays. They identify constraints that may allow better prediction and control of antibiotic resistance evolution.
- Andreas Porse
- , Leonie J. Jahn
- & Morten O. A. Sommer
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Article
| Open AccessStochastic pulsing of gene expression enables the generation of spatial patterns in Bacillus subtilis biofilms
Stochastic pulsing of gene expression can generate phenotypic diversity in a genetically identical population of cells. Here, the authors show that stochastic pulsing in the expression of a sigma factor enables the formation of spatial patterns in a multicellular system, Bacillus subtilis bacterial biofilms.
- Eugene Nadezhdin
- , Niall Murphy
- & James C. W. Locke
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Article
| Open AccessPlasmid-mediated metronidazole resistance in Clostridioides difficile
Cases of C. difficile (CD) resistant to metronidazole have been reported but the mechanism remains enigmatic. Here the authors identify a plasmid, which correlates with metronidazole resistance status in a large international collection of CD isolates, and demonstrate that the plasmid can confer metronidazole resistance.
- Ilse M. Boekhoud
- , Bastian V. H. Hornung
- & Wiep Klaas Smits
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Article
| Open AccessIntegrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei
Antibiotic-resistant bacteria are an urgent threat to human health. Here, Roberts et al. characterise and monitor an ongoing hospital outbreak of carbapenemase-producing Enterobacter hormaechei by integrating several technologies for whole-genome sequencing and shotgun metagenomics.
- Leah W. Roberts
- , Patrick N. A. Harris
- & Scott A. Beatson
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Article
| Open AccessA bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locus
Genedrives bias the inheritance of alleles in diploid organisms. Here, the authors develop a gene-drive analogous system for bacteria, selectively editing and clearing plasmids.
- J. Andrés Valderrama
- , Surashree S. Kulkarni
- & Ethan Bier
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| 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 AccessCoordination of cohabiting phage elements supports bacteria–phage cooperation
Bacterial pathogens often carry multiple phage-derived elements within their genome. Here, the authors show that two phage elements are co-regulated in Listeria monocytogenes, the first one controlling the induction of the second one, which in turn regulates virulence of their bacterial host.
- Tal Argov
- , Shai Ran Sapir
- & Anat A. Herskovits
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Article
| Open AccessMultisite phosphorylation drives phenotypic variation in (p)ppGpp synthetase-dependent antibiotic tolerance
Individual bacteria within isogenic populations can differ in antibiotic tolerance. Here, Libby et al. show that antibiotic tolerance variability can be driven by ‘noisy’ expression of a gene encoding a (p)ppGpp synthetase, which is in turn regulated by multisite phosphorylation of a transcription factor.
- Elizabeth A. Libby
- , Shlomi Reuveni
- & Jonathan Dworkin
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| 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 AccessPlasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development
New tuberculosis therapies, targeting respiratory chain components of Mycobacterium tuberculosis, are under development. Here the authors show that, contrary to common belief, some of these components are not essential for pathogen viability and/or virulence in animal models of infection.
- Tiago Beites
- , Kathryn O’Brien
- & Dirk Schnappinger
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| Open AccessProphages and satellite prophages are widespread in Streptococcus and may play a role in pneumococcal pathogenesis
Prophages are viral genomes integrated within bacterial genomes. Here, Rezaei Javan et al. identify nearly 800 prophages and satellite prophages in > 1300 Streptococcus genomes, and show that a satellite prophage is associated with virulence in a mouse model of pneumococcal infection.
- Reza Rezaei Javan
- , Elisa Ramos-Sevillano
- & Angela B. Brueggemann
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Article
| Open AccessDissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei
Shigella sonnei is one of the main species causing shigellosis worldwide. Here the authors analyse nearly 400 S. sonnei genome sequences and carry out experimental evolution experiments to shed light into the evolutionary processes underlying the recent emergence of fluoroquinolone resistance in this pathogen.
- Hao Chung The
- , Christine Boinett
- & Stephen Baker
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| Open AccessPhylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes
The second plague pandemic, caused by Yersinia pestis, started in the 14th century and recurred in Europe until the 18th century. Here, the authors reconstruct ancient Y. pestis genomes from human remains spanning this period, shedding light into the phylogeography and population structure of the European strains.
- Maria A. Spyrou
- , Marcel Keller
- & Johannes Krause
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| Open AccessAn African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation
Invasive non-typhoidal Salmonella (iNTS) infections are dominated by antibiotic resistant isolates of the sequence type (ST) 313. Here, the authors identify the ST313 sublineage II.1 in the Democratic Republic of the Congo exhibiting extensive drug resistance and genetic signatures potentially associated with host adaptation.
- Sandra Van Puyvelde
- , Derek Pickard
- & Stijn Deborggraeve
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| 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 AccessA role for antibiotic biosynthesis monooxygenase domain proteins in fidelity control during aromatic polyketide biosynthesis
Formicapyridines are similar to pentacyclic fasamycin and formicamycin aromatic polyketides but with a pyridine moiety. Here the authors rationally mutate the biosynthetic gene cluster to increase production and identify a non-catalytic role for the ABM superfamily of proteins.
- Zhiwei Qin
- , Rebecca Devine
- & Barrie Wilkinson
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Article
| Open AccessTwo-step chromosome segregation in the stalked budding bacterium Hyphomonas neptunium
In bacteria, DNA replication and segregation are commonly coupled. Here, by investigating the dynamics of these processes in the marine bacterium Hyphomonas neptunium, the authors unravel a two-step chromosomal segregation process reminiscent of eukaryotic mitosis, providing insights into the evolution of bacterial cell organization.
- Alexandra Jung
- , Anne Raßbach
- & Martin Thanbichler
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Article
| Open AccessGenomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages
Syphilis is caused by the bacterium Treponema pallidum subspecies pallidum (TPA), and incidence has risen recently in many countries. Here, Beale et al. provide whole-genome TPA sequences from 73 clinical samples and show how antimicrobial resistance emerged independently in circulating lineages.
- Mathew A. Beale
- , Michael Marks
- & Nicholas R. Thomson
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Article
| Open AccessZinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus
WalKR is an essential two-component regulator that controls peptidoglycan synthesis in the human pathogen Staphylococcus aureus. Here, the authors provide biochemical, structural, and functional evidence supporting that the binding of a zinc ion inhibits autophosphorylation and thus alters WalKR regulatory activity.
- Ian R. Monk
- , Nausad Shaikh
- & Timothy P. Stinear
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Article
| Open AccessDual pathways of tRNA hydroxylation ensure efficient translation by expanding decoding capability
5-carboxymethoxyuridine (cmo5U) is one of the RNA modifications found in bacterial tRNA anticodons. Here the authors show that the first step of cmo5U biosynthesis from uridine is mediated by either one of two parallel factors, TrhP or TrhO, and that cmo5U modification is required for efficient translation.
- Yusuke Sakai
- , Satoshi Kimura
- & Tsutomu Suzuki
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Article
| Open AccessHypervirulent Listeria monocytogenes clones’ adaption to mammalian gut accounts for their association with dairy products
Here, Maury et al. show that hypervirulent Listeria monocytogenes (Lm) clones associated to dairy products exhibit higher adaptation to the mammalian gut environment, while hypovirulent clones persist in food processing environment, suggesting a relationship between Lm pathogenic potential and niche adaptation.
- Mylène M. Maury
- , Hélène Bracq-Dieye
- & Marc Lecuit
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| Open AccessGWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions
Resistance to antibiotics hampers the treatment of infectious diseases such as tuberculosis (TB). Here, Farhat et al. perform genome-wide association testing for minimum inhibitory concentration (MIC) of 12 anti-TB drugs in whole-genome sequenced clinical M. tuberculosis isolates and identify 13 genomic loci.
- Maha R. Farhat
- , Luca Freschi
- & Megan Murray
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Article
| Open AccessA bacterial checkpoint protein for ribosome assembly moonlights as an essential metabolite-proofreading enzyme
Adventitious oxidation of erythrose-4-phosphate generates 4-phosphoerythronate, which is detoxified by metabolite-proofreading phosphatases in eukaryotes. Here, Sachla & Helmann show that a similar function is carried out in Bacillus subtilis by a checkpoint protein involved in ribosome assembly.
- Ankita J. Sachla
- & John D. Helmann
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| Open AccessIdentification and characterization of a direct activator of a gene transfer agent
Gene transfer agents (GTAs) are ‘domesticated’ bacteriophages that can transfer any genes between bacteria. Here, Paul Fogg identifies a protein that directly regulates transcription of GTA genes and whose expression is in turn controlled by a global cell-cycle regulator and a quorum-sensing regulator.
- Paul C. M. Fogg
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Article
| Open AccessGenome-wide association analyses of invasive pneumococcal isolates identify a missense bacterial mutation associated with meningitis
Meningitis is a severe form of invasive pneumococcal disease (IPD). To study the contribution of bacterial genomic variation, here Li et al. perform whole genome sequencing of pneumococcal isolates from IPD patients and identify an association for higher risk of meningitis with a pbp1bA641C variant
- Yuan Li
- , Benjamin J. Metcalf
- & Bernard W. Beall
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Article
| Open AccessAntibiotic sensitivity reveals that wall teichoic acids mediate DNA binding during competence in Bacillus subtilis
Natural genetic transformation in bacteria requires DNA binding at the surface of competent cells. Here, Mirouze et al. show that wall teichoic acids are specifically produced or modified during competence in Bacillus subtilis and promote (directly or indirectly) DNA binding at the cell surface.
- Nicolas Mirouze
- , Cécile Ferret
- & Rut Carballido-López
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Article
| Open AccessProteolysis of histidine kinase VgrS inhibits its autophosphorylation and promotes osmostress resistance in Xanthomonas campestris
Bacterial histidine kinases (HKs) play key roles in the response to stimuli and are regulated by reversible phosphorylation. Here, the authors show that the activity of a HK in the plant pathogen Xanthomonas campestris is modulated by irreversible, proteolytic modification in response to osmostress.
- Chao-Ying Deng
- , Huan Zhang
- & Wei Qian
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Article
| Open AccessStructural basis for the recognition of sulfur in phosphorothioated DNA
DNA phosphorothioation (PT-DNA) is a DNA backbone sulfur modification that is recognized by the type-IV restriction endonuclease ScoMcrA. Here the authors provide insights into sulfur recognition by solving the crystal structure of the PT-DNA bound sulfur-binding domain (SBD) from ScoMcrA and they further show that SBD homologs are widely spread among prokaryotes.
- Guang Liu
- , Wencheng Fu
- & Xinyi He
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Article
| Open AccessGene inversion potentiates bacterial evolvability and virulence
Head-on replication-transcription collisions occur within genes encoded on the lagging DNA strand. Here, the authors show that a large number of originally co-oriented (leading strand) genes have inverted to the head-on orientation, increasing both gene-specific mutation rates, and the overall evolvability of several bacterial pathogens.
- Christopher N. Merrikh
- & Houra Merrikh
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Article
| Open AccessMachine learning and structural analysis of Mycobacterium tuberculosis pan-genome identifies genetic signatures of antibiotic resistance
Mycobacterium tuberculosis exhibits complex evolution of antimicrobial resistance (AMR). Here, the authors perform machine learning and structural analysis to identify signatures of AMR evolution to 13 antibiotics.
- Erol S. Kavvas
- , Edward Catoiu
- & Bernhard O. Palsson
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Article
| Open AccessCrystal structure of TcpK in complex with oriT DNA of the antibiotic resistance plasmid pCW3
Conjugative transfer of antibiotic resistance plasmid pCW3 in Clostridium perfringens is mediated by the tcp locus. Here, the authors identify a wHTH-type protein, TcpK, that is essential for efficient plasmid transfer and interacts with the plasmid oriT region in a unique manner.
- Daouda A. K. Traore
- , Jessica A. Wisniewski
- & James C. Whisstock
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Article
| Open AccessPopulation genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination
Since the 1980s, hypervirulent clonal-group CG23 serotype K1 Klebsiella pneumoniae has been recognised as a prominent cause of community-acquired liver abscess and other severe infections. Here, the authors investigate the genomic evolutionary history of CG23 and suggest a new reference strain for CG23.
- Margaret M. C. Lam
- , Kelly L. Wyres
- & Kathryn E. Holt
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Article
| Open AccessPooled CRISPR interference screening enables genome-scale functional genomics study in bacteria with superior performance
Systemic investigation of the bacterial genome is essential for both basic microbiology and bioengineering. Here the authors demonstrate CRISPRi pooled screening as a high-throughput tool for identifying gene and phenotype associations in bacteria.
- Tianmin Wang
- , Changge Guan
- & Xin-Hui Xing
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Article
| Open AccessAnalysis of 3800-year-old Yersinia pestis genomes suggests Bronze Age origin for bubonic plague
Yersinia pestis has caused infections (plague) in humans since the Early Bronze Age (5000 years ago). Here, Spyrou et al. reconstruct Y. pestis genomes from Late Bronze Age individuals, and find genomic evidence compatible with flea-mediated transmission causing bubonic plague.
- Maria A. Spyrou
- , Rezeda I. Tukhbatova
- & Johannes Krause
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Article
| Open AccessRegulatory protein SrpA controls phage infection and core cellular processes in Pseudomonas aeruginosa
You et al. show that SrpA, a small protein widely conserved among bacteria, controls core cellular processes in response to phage infection and environmental signals in Pseudomonas aeruginosa, including cell motility, chemotaxis, biofilm formation, and virulence.
- Jiajia You
- , Li Sun
- & Hongjiang Yang
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Article
| Open AccessCulturing of female bladder bacteria reveals an interconnected urogenital microbiota
The female bladder seems to harbor a poorly characterized indigenous microbiota. Here, the authors isolate and genome-sequence 149 bacterial strains from catheterized urine of 77 women, generating a culture collection representing two thirds of the bacterial diversity within the samples.
- Krystal Thomas-White
- , Samuel C. Forster
- & Trevor D. Lawley
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Article
| Open AccessBiochemical mechanisms determine the functional compatibility of heterologous genes
Sequence composition is thought to be a major factor governing the functionality of horizontally transferred genes. In contrast, Porse et al. show that phylogenetic origin, and the type of resistance mechanism, are major factors affecting the functionality of horizontally transferred antibiotic resistance genes.
- Andreas Porse
- , Thea S. Schou
- & Morten O. A. Sommer
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Article
| Open AccessSensory deprivation in Staphylococcus aureus
Bacteria use two-component systems (TCSs) to sense and respond to environmental changes. Here, the authors show that Staphylococcus aureus can survive in the absence of all its 16 TCSs under growth arrest conditions, and each TCS seems to be sufficient to sense and respond to specific environmental clues.
- Maite Villanueva
- , Begoña García
- & Iñigo Lasa