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Unencapsulated Streptococcus pneumoniae from conjunctivitis encode variant traits and belong to a distinct phylogenetic cluster
Pneumococci can cause a variety of bacterial infections including conjunctivitis. Here, Valentino et al.show that most conjunctivitis-causing pneumococci belong to a closely related group of strains that possess a unique set of putative virulence factors.
- Michael D. Valentino
- , Abigail Manson McGuire
- & Michael S. Gilmore
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The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors
Genes encoding two pore-forming toxins (γ-haemolysins HlgAB and HlgCB) are present in almost all human Staphylococcus aureus isolates. Here Spaan et al.show that HlgAB and HlgCB target different phagocyte types by interacting with specific chemokine receptors and complement receptors, respectively.
- András N. Spaan
- , Manouk Vrieling
- & Thomas Henry
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Versatile in vitro system to study translocation and functional integration of bacterial outer membrane proteins
The mechanisms of protein translocation across and integration into bacterial outer membranes are poorly understood. Here, Norell et al. reconstitute type-V secretion and β-barrel protein biogenesis in proteoliposomes providing a versatile cell-free system to study integration and translocation.
- Derrick Norell
- , Alexander Heuck
- & Enguo Fan
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Covalently linked hopanoid-lipid A improves outer-membrane resistance of a Bradyrhizobium symbiont of legumes
Lipopolysaccharides (LPSs) in the outer membrane of Gram-negative bacteria play key roles in the microbial interactions with animals and plants. Here the authors identify a unique LPS with a covalently-attached hopanoid moiety that contributes to membrane stability in a bacterial symbiont of legumes.
- Alba Silipo
- , Giuseppe Vitiello
- & Antonio Molinaro
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Evolutionary expansion of a regulatory network by counter-silencing
Genes acquired by horizontal transfer must be incorporated into existing regulatory networks to become functional. Here, Will et al. show that conserved and horizontally acquired PhoP-regulated genes in Salmonellaare regulated by distinct mechanisms, defined by promoter architecture.
- W. Ryan Will
- , Denise H. Bale
- & Ferric C. Fang
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| Open AccessA random six-phase switch regulates pneumococcal virulence via global epigenetic changes
Pneumococci can alternate between harmless and highly virulent forms. Here the authors show that such variation may be due to random rearrangements in a genetic locus encoding a restriction-modification system, resulting in epigenetic changes that affect expression of many genes.
- Ana Sousa Manso
- , Melissa H. Chai
- & Marco R. Oggioni
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Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins
Pore-forming toxins secreted by pathogenic bacteria attack target cells by forming openings that span the plasma membrane. Here, Yamashita et al. shed light on the mechanism of pore assembly by solving the crystal structures of two staphylococcal toxins in their prepore conformations.
- Daichi Yamashita
- , Takaki Sugawara
- & Min Yao
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High-resolution structure of the Shigella type-III secretion needle by solid-state NMR and cryo-electron microscopy
Solving structures of large protein complexes remains a significant challenge for structural biologists. Demers et al. determine the atomic structure of a Shigellatype-III secretion system using a Rosetta-based modelling strategy that draws on both solid-state NMR and cryo-electron microscopy data sets.
- Jean-Philippe Demers
- , Birgit Habenstein
- & Nikolaos G. Sgourakis
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Vibrio cholerae use pili and flagella synergistically to effect motility switching and conditional surface attachment
Vibrio cholerae require flagella and mannose-sensitive hemagglutinin pili to attach to surfaces and form biofilms. Here Utada et al.find that flagella and pili act synergistically to mechanically scan a surface before irreversibly attaching via the pili.
- Andrew S. Utada
- , Rachel R. Bennett
- & Gerard C. L. Wong
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Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli
The ferric uptake regulator, Fur, is involved in the transcriptional regulation of iron metabolism. Here the authors show that Fur exhibits genome-wide regulatory effects in Escherichia colithat control many fundamental cellular processes linked to iron metabolism.
- Sang Woo Seo
- , Donghyuk Kim
- & Bernhard O. Palsson
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Pseudomonas aeruginosa adaptation in the nasopharyngeal reservoir leads to migration and persistence in the lungs
Pseudomonas aeruginosa causes chronic infections in patients with lung damage. Here, Fothergill et al. develop an intranasal inhalation model of P. aeruginosainfection and describe genetic and phenotypic changes that the bacteria undergo during adaptation and spread through the respiratory tract.
- Joanne L. Fothergill
- , Daniel R. Neill
- & Aras Kadioglu
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Cultivation-based multiplex phenotyping of human gut microbiota allows targeted recovery of previously uncultured bacteria
Research on the roles played by gut microbes in human health is hampered by our inability to isolate and study them in pure cultures. Here, the authors describe an approach that allows targeted cultivation and rapid characterization of a significant proportion of human gut bacteria.
- Elizabeth A. Rettedal
- , Heidi Gumpert
- & Morten O.A. Sommer
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Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin
Mycobacterium tuberculosis acquires iron from its host by producing iron-binding siderophores and by recruiting host transferrin to the phagosome. Here, Boradia et al. show that the bacterial GAPDH protein binds transferrin and drives the uptake of this host protein into M. tuberculosiscells.
- Vishant Mahendra Boradia
- , Himanshu Malhotra
- & Chaaya Iyengar Raje
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Clustering in community structure across replicate ecosystems following a long-term bacterial evolution experiment
It is unclear how predictable adaptive evolution is in multispecies ecosystems. Here, the authors show that relative abundance of bacterial species varies after long-term evolution, but that the final community composition clusters within a few types, which suggests that evolution follows only a few paths.
- Hasan Celiker
- & Jeff Gore
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| Open AccessCooperative secretions facilitate host range expansion in bacteria
Understanding the factors determining pathogen host range is critical for human health. Here, the authors show that bacteria use cooperative secretions to modify their environment and to infect multiple host species, which suggests that cooperative secretions are key determinants of host range in bacteria.
- Luke McNally
- , Mafalda Viana
- & Sam P. Brown
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| Open AccessStreptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline
Group B streptococci (GBS) started causing serious infections in newborn babies in the 1960s. Here, the authors show that the emergence of GBS diseases was associated with worldwide dissemination of a few clones that were resistant to tetracycline, an antibiotic that became widely used in the 1950s.
- Violette Da Cunha
- , Mark R. Davies
- & Philippe Glaser
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The bacterial metabolite 2-aminoacetophenone promotes association of pathogenic bacteria with flies
Certain bacterial metabolites can affect insect behaviour, but the underlying mechanisms are unclear. Here, the authors show that 2-aminoacetophenone, produced by the opportunistic human pathogen Pseudomonas aeruginosa, attracts flies and facilitates microbial dissemination and colonization of the fly gut.
- Stefania-Elisavet Kapsetaki
- , Ilias Tzelepis
- & Yiorgos Apidianakis
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Dispersed cells represent a distinct stage in the transition from bacterial biofilm to planktonic lifestyles
Bacteria can grow as free living planktonic cells or as part of surface-associated biofilms. Here the authors show, for the opportunistic pathogen Pseudomonas aeruginosa, that cells recently dispersed from biofilms are physiologically different from, and more virulent than, planktonic and biofilm cells.
- Song Lin Chua
- , Yang Liu
- & Liang Yang
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| Open AccessG1-arrested newborn cells are the predominant infectious form of the pathogen Brucella abortus
Certain pathogenic bacteria such as Brucella abortus undergo a temporary non-proliferative stage after infecting host cells. Here, the authors study chromosomal replication and segregation in B. abortusduring infection, showing that the non-proliferative stage consists of G1-arrested newborn cells.
- Michaël Deghelt
- , Caroline Mullier
- & Xavier De Bolle
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Opposing effects of target overexpression reveal drug mechanisms
Overexpression of a drug’s molecular target increases drug resistance in some cases. Here the authors show that overexpressing antibiotic targets in Escherichia colican cause positive and negative changes in drug resistance, depending on whether the drug induces harmful reactions involving its target.
- Adam C. Palmer
- & Roy Kishony
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Isocitrate lyase mediates broad antibiotic tolerance in Mycobacterium tuberculosis
Mycobacterium tuberculosisis intrinsically resistant to most antibiotics. Here, the authors show that the pathogen’s tolerance to three antibiotics, each one targeting a distinct cellular process, is mediated by an antioxidant response that requires the activation of isocitrate lyases.
- Madhumitha Nandakumar
- , Carl Nathan
- & Kyu Y. Rhee
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| Open AccessMolecular basis for bacterial peptidoglycan recognition by LysM domains
Proteins containing LysM domains recognize polysaccharides such as chitin and peptidoglycan, the main components of fungal and bacterial cell walls. Here the authors describe the molecular interactions between peptidoglycan and a LysM domain from the opportunistic bacterial pathogen Enterococcus faecalis.
- Stéphane Mesnage
- , Mariano Dellarole
- & Michael P. Williamson
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A mortise–tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes
Bacterial autotransporters are folded in a process that entraps segments of their N-terminal passenger domain. Here, Leyton et al. identify glycine-aromatic mortise and tenon motifs that mediate the passenger domain’s translocation to the bacterial cell surface, and show that the motifs are evolutionarily conserved.
- Denisse L. Leyton
- , Matthew D. Johnson
- & Trevor Lithgow
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| Open AccessFtsZ-independent septal recruitment and function of cell wall remodelling enzymes in chlamydial pathogens
Chlamydiae lack a conventional peptidoglycan cell wall, and yet cell wall remodelling enzymes are largely conserved in these organisms. Frandi et al.identify a chlamydial peptidoglycan endopeptidase, NlpD, and show that it targets the septum of dividing Chlamydiae in a manner dependent on cell wall synthesis.
- Antonio Frandi
- , Nicolas Jacquier
- & Patrick H. Viollier
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| Open AccessAmiA is a penicillin target enzyme with dual activity in the intracellular pathogen Chlamydia pneumoniae
Penicillin inhibits growth of chlamydial pathogens despite their lack of a conventional peptidoglycan cell wall. Here the authors report that the chlamydial amidase, AmiA, which can rescue cell division defects of an E. coli amiAmutant, has dual activity as a penicillin sensitive, lipid II-targetting carboxypeptidase.
- Anna Klöckner
- , Christian Otten
- & Beate Henrichfreise
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| Open AccessNitrogen stress response and stringent response are coupled in Escherichia coli
The nitrogen regulation stress response and the stringent response are two major regulatory pathways in bacteria, but their mutual coordination is unclear. Here, the authors show that NtrC, the main regulatory protein from the first pathway, activates expression of relA, a key gene from the second pathway.
- Daniel R. Brown
- , Geraint Barton
- & Sivaramesh Wigneshweraraj
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| Open AccessCell cycle transition from S-phase to G1 in Caulobacter is mediated by ancestral virulence regulators
The bacterium Caulobacter crescentus divides asymmetrically to generate a replicative stalk cell and a quiescent swarmer cell. Fumeaux et al. show that MucR zinc-finger transcription factors, which regulate virulence in other species, also control re-entry into quiescence in Caulobacter.
- Coralie Fumeaux
- , Sunish Kumar Radhakrishnan
- & Patrick H. Viollier
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Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population
Synonymous mutations, nucleotide changes that do not alter the encoded amino acid, are usually seen not to have an effect on organism survival. Here, Bailey et al. show that two synonymous mutations in Pseudomonas fluorescenshad a beneficial effect and acted via increased gene expression.
- Susan F. Bailey
- , Aaron Hinz
- & Rees Kassen
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Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences
Phosphorothioate (PT) DNA modifications are widespread in bacteria and play a critical role in cell physiology. Here, the authors develop two sequence-based technologies to map PT modifications across bacterial genomes.
- Bo Cao
- , Chao Chen
- & Peter C. Dedon
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| Open AccessIntegrating artificial with natural cells to translate chemical messages that direct E. coli behaviour
The control of cellular behaviour largely relies on genetic engineering, but artificial cells could be designed to control cell processes through chemical communication. Here, the authors develop an artificial cell that is able to translate a chemical message into a signal that can be sensed by E. coliand activate a cellular response.
- Roberta Lentini
- , Silvia Perez Santero
- & Sheref S. Mansy
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Persistent super-diffusive motion of Escherichia coli chromosomal loci
In bacteria, chromosomal architecture exhibits spatial and temporal fluctuations, which affect cellular functions. Here, Javer et al. use high-resolution tracking of chromosomal loci in E. colito uncover rare events of unusually large and fast movements, providing new insight into bacterial chromosome dynamics.
- Avelino Javer
- , Nathan J. Kuwada
- & Marco Cosentino Lagomarsino
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| Open AccessMobile elements drive recombination hotspots in the core genome of Staphylococcus aureus
Horizontal gene transfer occurs in most bacteria, yet it is unclear whether it happens in clonal species. Here, Everitt et al. show widespread within-species recombination, driven by mobile elements, in the genome of the pathogen Staphylococcus aureus, but no recombination between closely related strains.
- Richard G. Everitt
- , Xavier Didelot
- & Daniel J. Wilson
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| Open AccessPhysiological and genomic features of highly alkaliphilic hydrogen-utilizing Betaproteobacteria from a continental serpentinizing site
Microbes can dwell in highly alkaline environments in the absence of obvious food sources. Here, the authors describe physiological and genomic features of a group of bacteria that live on hydrogen, calcium carbonate and oxygen at a very high pH.
- Shino Suzuki
- , J. Gijs Kuenen
- & Kenneth H. Nealson
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The curved shape of Caulobacter crescentus enhances surface colonization in flow
The potential advantages of specific cell shapes among microbes are unclear. Here, the authors show that the curved shape of the bacterium Caulobacter crescentus, which lives in lakes and streams, helps cells to colonize surfaces in the presence of fluid flow.
- Alexandre Persat
- , Howard A. Stone
- & Zemer Gitai
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Structural basis of PcsB-mediated cell separation in Streptococcus pneumoniae
The peptidoglycan hydrolase PcsB is required for cell wall splitting during cell division in Streptococci. Bartual et al.show that PcsB adopts an autoinhibited dimeric structure, and demonstrate the muralytic activity of the uninhibited catalytic domain.
- Sergio G. Bartual
- , Daniel Straume
- & Juan A. Hermoso
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Bacterial twitching motility is coordinated by a two-dimensional tug-of-war with directional memory
Bacteria such as Neisseria gonorrhoeaeuse filamentous appendages known as pili to move on surfaces. Here, using a combined theoretical and experimental approach, the authors show that pili are coordinated through a tug-of-war mechanism that provides directional persistence.
- Rahul Marathe
- , Claudia Meel
- & Stefan Klumpp
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| Open AccessMutation rate plasticity in rifampicin resistance depends on Escherichia coli cell–cell interactions
The factors varying mutation rate at a particular site in a single genotype remain elusive. Here, Krašovec et al. show that mutation rates at sites conferring resistance to rifampicin in Escherichia coli decrease with population density, and that mutation-rate plasticity is controlled by the luxSgene.
- Rok Krašovec
- , Roman V. Belavkin
- & Christopher G. Knight
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Crystal structure of listeriolysin O reveals molecular details of oligomerization and pore formation
The cytolysin, listeriolysin O (LLO), is expressed by Listeria and forms pores in the phagosomal membrane in response to decreased pH. Here, Yildiz et al. solve the crystal structure of LLO, identify residues that serve as the pH sensor, and determine the mechanism of pore formation in host membranes.
- Stefan Köster
- , Katharina van Pee
- & Özkan Yildiz
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MicroRNA-302b augments host defense to bacteria by regulating inflammatory responses via feedback to TLR/IRAK4 circuits
Bacterial infection stimulates a powerful inflammatory response that must be regulated to prevent tissue damage. Zhou et al.identify microRNA-302b as a feedback suppressor of inflammatory signalling that alleviates lung injury following Pseudomonas infection by targeting the NF-κB activator IRAK4.
- Xikun Zhou
- , Xuefeng Li
- & Min Wu
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An RNA-seq method for defining endoribonuclease cleavage specificity identifies dual rRNA substrates for toxin MazF-mt3
MazF toxins inhibit bacterial growth by cleaving single-stranded RNA at specific sequences. Here, the authors describe a new genome-wide approach, MORE RNA-seq, for defining MazF cleavage specificity, and show that MazF-mt3 cleaves 23S and 16S ribosomal RNAs.
- Jason M. Schifano
- , Irina O. Vvedenskaya
- & Nancy A Woychik
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| Open AccessCell wall precursors are required to organize the chlamydial division septum
Cell division in Chlamydiales remains mysterious as it occurs in the absence of a cytokinetic tubulin and a classical peptidoglycan cell wall. Jacquier et al. show that the actin homologue MreB is recruited to the division site in Waddliaand that this depends on synthesis of the peptidoglycan precursor lipid II.
- Nicolas Jacquier
- , Antonio Frandi
- & Gilbert Greub
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Lactate racemase is a nickel-dependent enzyme activated by a widespread maturation system
Lactate racemase is an enzyme that interconverts the L and D isomers of the common metabolite lactate. Here, the authors show that lactate racemase represents a new type of nickel-dependent enzyme, which is activated by accessory proteins that are widespread among prokaryotic microbes.
- Benoît Desguin
- , Philippe Goffin
- & Pascal Hols
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| Open AccessThe Vibrio cholerae type VI secretion system employs diverse effector modules for intraspecific competition
Some strains of the pathogen Vibrio choleraecan kill each other by injecting effector proteins that are toxic in the absence of cognate ‘immunity’ proteins. Here, the authors show that strains with high pathogenic potential possess matching effector-immunity sets and can coexist.
- Daniel Unterweger
- , Sarah T. Miyata
- & Stefan Pukatzki
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| Open AccessThe actin homologue MreB organizes the bacterial cell membrane
The formation of lipid domains in eukaryotic cells is controlled by the cortical actin cytoskeleton. Here, the authors show that the bacterial actin homologue MreB has a comparable activity, influencing the formation of regions of increased fluidity that determine the distribution of membrane proteins.
- Henrik Strahl
- , Frank Bürmann
- & Leendert W. Hamoen
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| Open AccessDelayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism
The delayed onset of bactericidal activity of the anti-tuberculosis antibiotic bedaquiline is puzzling. Here, Koul and colleagues show, using a multi-omics approach, that the drug triggers a metabolic remodelling in Mycobacterium tuberculosisthat enables the pathogen’s transient survival.
- Anil Koul
- , Luc Vranckx
- & Dirk Bald
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Electron uptake by iron-oxidizing phototrophic bacteria
Little is known about extracellular electron uptake by microbes. Here Bose et al. show that the anoxygenic photoautotroph Rhodopseudomonas palustrisTIE-1 accepts electrons from a poised electrode, which can be uncoupled from photosynthesis, and the pioABC system has a role in this uptake.
- A. Bose
- , E.J. Gardel
- & P.R. Girguis
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An asymmetric heterodomain interface stabilizes a response regulator–DNA complex
Bacterial two-component systems relay extracellular signals to transcriptional networks via response regulators. Narayanan et al.present structures of the response regulator KdpE bound to DNA, and show that asymmetric interactions between the receiver and DNA-binding domains are required to sustain gene expression.
- Anoop Narayanan
- , Shivesh Kumar
- & Dinesh A. Yernool
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Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol
Organisms can adapt to environmental change but how this affects metabolism is unclear. Here, the authors provide a detailed analysis of the effects of individual adaptive mutations on the metabolic network in E. coli, and find evidence of metabolic reprogramming during laboratory evolution on glycerol.
- Kian-Kai Cheng
- , Baek-Seok Lee
- & Martin Robert
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Autotransporters but not pAA are critical for rabbit colonization by Shiga toxin-producing Escherichia coli O104:H4
An outbreak of diarrhoea and haemolytic uraemic syndrome in Germany in 2011 was caused by a Shiga toxin-producing enteroaggregative E. coli, which carried the aggregative adherence plasmid pAA. Here, the authors show that autotransporters, but not pAA, are required for intestinal colonization in an infant rabbit model.
- Diana Munera
- , Jennifer M. Ritchie
- & Matthew K. Waldor
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