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| Open AccessExtracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection
Pathogenic agents can spread from an initial to a secondary site via the lymphatics. Here, using a mouse model of infection, the authors show that S. pyogenes readily transit through sequential lymph nodes within efferent lymphatics to reach the bloodstream and drive systemic infection, while remaining extracellular.
- Matthew K. Siggins
- , Nicola N. Lynskey
- & Shiranee Sriskandan
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Article
| Open AccessThe Bartonella autotransporter BafA activates the host VEGF pathway to drive angiogenesis
Pathogenic bacteria of the genus Bartonella can induce vasoproliferative lesions during infection. Here, Tsukamoto et al. show that this effect is caused by a secreted protein that induces cell proliferation and angiogenesis by acting as an analog of the host’s vascular endothelial growth factor (VEGF).
- Kentaro Tsukamoto
- , Naoaki Shinzawa
- & Yohei Doi
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Article
| Open AccessThe minimal meningococcal ProQ protein has an intrinsic capacity for structure-based global RNA recognition
FinO-domain proteins are bacterial RNA-binding proteins with a wide range of target specificities. Here, the authors employ UV CLIP-seq and show that minimal ProQ protein of Neisseria meningitidis binds to various small non-coding RNAs and mRNAs involved in virulence.
- Saskia Bauriedl
- , Milan Gerovac
- & Christoph Schoen
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Article
| Open AccessInvasion of vaginal epithelial cells by uropathogenic Escherichia coli
Uropathogenic E. coli can adhere to vaginal epithelial cells preceding urinary tract infection (UTI). Here, Brannon et al. show that urinary E. coli isolates can not only adhere to, but also invade vaginal cells in mouse UTI models and in clinical samples obtained from women with recurrent UTI.
- John R. Brannon
- , Taryn L. Dunigan
- & Maria Hadjifrangiskou
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Article
| Open AccessDecoding the stoichiometric composition and organisation of bacterial metabolosomes
Enteric pathogens such as Salmonella depend on propanediol-utilising microcompartments (Pdu MCP), which self-assemble from cytosolic proteins. Using mass spectrometry-based absolute quantification, the authors here define the protein stoichiometry and propose an organizational model of a Salmonella Pdu MCP.
- Mengru Yang
- , Deborah M. Simpson
- & Lu-Ning Liu
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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 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 AccessHydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis
The importance of host-produced hydrogen sulfide (H2S) in microbial pathogenesis is poorly understood. Here, Saini et al. show that H2S alters Mycobacterium tuberculosis (Mtb) central metabolism, stimulates respiration to promote growth and TB disease, and upregulates the Dos regulon.
- Vikram Saini
- , Krishna C. Chinta
- & Adrie J. C. Steyn
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Article
| Open AccessThe C. difficile toxin B membrane translocation machinery is an evolutionarily conserved protein delivery apparatus
Large Clostridial toxins infiltrate host cells using a translocation domain (LCT-T). Here, using a genomics-driven approach and functional assays, the authors uncover the presence of distant LCT-T homologs in bacteria outside clostridia and provide evidence for a toxic effector function in the gammaproteobacterium Serratia marcescens.
- Kathleen E. Orrell
- , Michael J. Mansfield
- & Roman A. Melnyk
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Article
| Open AccessCervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
Ureaplasma parvum is often isolated from intrauterine infections, which are associated with 40% of preterm births. Here, Pavlidis et al. present a mouse model of ascending U. parvum infection that resembles human disease, and show that mild cervical damage promotes intrauterine infection, inflammation and preterm birth.
- Ioannis Pavlidis
- , Owen B. Spiller
- & Sarah J. Stock
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Article
| Open AccessPathogen-targeting glycovesicles as a therapy for salmonellosis
Antibiotic therapy is usually not effective for salmonellosis. Here, the authors present an approach that may be useful for the treatment of salmonellosis, consisting of hydrogen sulfide (H2S)-responsive glycovesicles that release antibiotics in the presence of Salmonella in the gut.
- Haibo Mu
- , Hu Bai
- & Jinyou Duan
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Article
| Open AccessMolecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections
Necrotizing soft tissue infections (NSTIs) are caused by a single pathogen such as Streptococcus pyogenes or by multiple bacterial species. Here, the authors integrate microbial community profiling with host and pathogen transcriptional analysis in patient biopsies, and identify an interferon-related signature specific to S. pyogenes NSTIs.
- Robert Thänert
- , Andreas Itzek
- & Dietmar H. Pieper
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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 AccessUrinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes
Acinetobacter baumannii is generally considered an opportunistic pathogen. Here, Di Venanzio et al. develop a mouse model of catheter-associated urinary tract infection and show that a plasmid confers niche specificity to an A. baumannii urinary isolate by regulating the expression of chromosomal genes.
- Gisela Di Venanzio
- , Ana L. Flores-Mireles
- & Mario F. Feldman
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Article
| Open AccessStructural basis for the homotypic fusion of chlamydial inclusions by the SNARE-like protein IncA
Chlamydia trachomatis forms membrane-bound inclusions inside the host cell that are decorated with IncA, a SNARE-like protein that promotes the fusion of inclusions. Here, Cingolani et al. show that the protein folds into a non-canonical four-helix bundle and identify an intramolecular clamp required for membrane fusion.
- Gino Cingolani
- , Michael McCauley
- & Fabienne Paumet
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Article
| Open AccessEnvironmental pH and peptide signaling control virulence of Streptococcus pyogenes via a quorum-sensing pathway
The mechanism by which environmental pH controls the virulence of the pathogen Streptococcus pyogenes is unclear. Here, Do et al. show that changes in pH affect the activity of the virulence regulator RopB via its interaction with a quorum-sensing peptide signal.
- Hackwon Do
- , Nishanth Makthal
- & Muthiah Kumaraswami
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Article
| Open AccessUnique structural features of a bacterial autotransporter adhesin suggest mechanisms for interaction with host macromolecules
Autotransporter proteins are localised to the bacterial surface and promote colonisation of host epithelial surfaces. Here, the authors present the crystal structure of autotransporter UpaB and show evidence for distinct binding sites for glycosaminoglycans and host fibronectin.
- Jason J. Paxman
- , Alvin W. Lo
- & Begoña Heras
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| Open AccessCritical role of bacterial dissemination in an infant rabbit model of bacillary dysentery
The bacterial pathogen Shigella flexneri causes bacillary dysentery (bloody diarrhoea). Here, Yum et al. present an infant rabbit model of S. flexneri infection that recapitulates human disease symptoms and features bacterial dissemination as an essential determinant of pathogenesis.
- Lauren K. Yum
- , Mariana X. Byndloss
- & Hervé Agaisse
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| Open AccessChronic Chlamydia infection in human organoids increases stemness and promotes age-dependent CpG methylation
Chronic infections of the fallopian tubes with Chlamydia trachomatis can cause scarring and infertility. Here, the authors show that the pathogen alters stem cell differentiation and DNA methylation in human fallopian tube organoids, suggesting a potential link to cellular ageing and malignant transformation.
- Mirjana Kessler
- , Karen Hoffmann
- & Thomas F. Meyer
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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 AccessTGFβ/BMP immune signaling affects abundance and function of C. elegans gut commensals
Host genetics modulates gut microbiota composition, which in turn affects host health, but little is known about the specific genes involved. Here, Berg et al. show that TGFβ/BMP immune signalling affects abundance and function of commensal Enterobacter species in C. elegans.
- Maureen Berg
- , David Monnin
- & Michael Shapira
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Article
| Open AccessApoptosis of intestinal epithelial cells restricts Clostridium difficile infection in a model of pseudomembranous colitis
The enterotoxins TcdA and TcdB induce cytotoxicity of epithelial cells during Clostridium difficile infection. Here the authors show that bacterial induced epithelial cell death occurs via activation of caspases 3 and 7, resulting in apoptotic cell death.
- Pedro H. V. Saavedra
- , Linyan Huang
- & Mohamed Lamkanfi
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| Open AccessVibrio cholerae motility exerts drag force to impede attack by the bacterial predator Bdellovibrio bacteriovorus
Prey bacteria have evolved different strategies to counteract predation but the genetic basis remains unclear. Here, Duncan et al. identify key genes involved in Vibrio cholerae sensitivity to Bdellovibrio bacteriovorus predation, providing new insights into prey resistance mechanisms.
- Miles C. Duncan
- , John C. Forbes
- & Andrew Camilli
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Article
| Open AccessMicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy
How Mycobacterium tuberculosis (Mtb) escapes autophagy-mediated clearance is poorly understood. Here, Liu et al. show that Mtb-induced MicroRNA-27a targets the ER-associated calcium transporter CACNA2D3, leading to suppression of antimicrobial autophagy and to enhanced intracellular survival of Mtb.
- Feng Liu
- , Jianxia Chen
- & Baoxue Ge
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Article
| Open AccessA mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
Animal models of group-B streptococcal infections are needed to develop effective therapies. Here, Andrade et al. present a mouse model in which the bacteria are transmitted from vaginally colonised pregnant females to their offspring, causing neonatal meningitis and neurological developmental disabilities.
- Elva Bonifácio Andrade
- , Ana Magalhães
- & Paula Ferreira
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| Open AccessEvolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa
Mutations in gene pmrB are found in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Here, Bricio-Moreno et al. show in a mouse model of respiratory infection that the mutations enhance bacterial adherence to epithelial cells and resistance to lysozyme, but also increase antibiotic susceptibility.
- Laura Bricio-Moreno
- , Victoria H. Sheridan
- & Daniel R. Neill
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Article
| Open AccessHuman macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity
M1 and M2 cells are representative of proinflammatory versus resolving macrophages, respectively. Here the authors characterize the lipid mediator response to bacterial infection by these cells and show that differing panels of leukotrienes and specialized pro-resolving mediators contribute to control of the dichotomy.
- Oliver Werz
- , Jana Gerstmeier
- & Charles N. Serhan
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Article
| Open AccessCooperative interactions between seed-borne bacterial and air-borne fungal pathogens on rice
Interactions between bacteria and fungi are common and contribute to ecosystem processes. Here, Jung et al. show that the interaction between two plant pathogens (a seed-borne bacterium and an air-borne fungus) promotes their own survival and dispersal, as well as disease progression on rice plants.
- Boknam Jung
- , Jungwook Park
- & Jungkwan Lee
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Article
| Open AccessLipoteichoic acid deficiency permits normal growth but impairs virulence of Streptococcus pneumoniae
Teichoic acid is bound to peptidoglycan (wall teichoic acid, WTA) or to membrane glycolipids (lipoteichoic acid, LTA) in most Gram-positive bacteria. Here, the authors identify a putative ligase required for the assembly of LTA, but not WTA, and important for Streptococcus pneumoniae virulence in mouse models.
- Nathalie Heß
- , Franziska Waldow
- & Nicolas Gisch
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Article
| Open AccessThe metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella
The enzyme fructose-bisphosphate aldolase (FBA) plays central roles in glycolysis and gluconeogenesis. Here, Ziveri et al. show that FBA of the pathogen Francisella novicida acts, in addition, as a transcriptional regulator and is important for bacterial multiplication in macrophages.
- Jason Ziveri
- , Fabiola Tros
- & Alain Charbit
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Article
| Open AccessStructural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures
Understanding of the mycobacterial transcription system is useful to the development of therapeutics against tuberculosis infection. Here the authors present the crystal structure of a completeM. smegmatisRNA polymerase open promoter complex that reveals unique features of the mycobacterial polymerase.
- Elizabeth A. Hubin
- , Mirjana Lilic
- & Elizabeth A. Campbell
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Article
| Open AccessStrength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4
Neisseria meningitidis bacteria bind to host proteins CD147 and β2-adrenergic receptor on the surface of endothelial cells. Here, Maïssa et al. show that the two proteins interact with each other forming clusters that increase the binding strength of the bacteria to endothelial cells.
- Nawal Maïssa
- , Valentina Covarelli
- & Sandrine Bourdoulous
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Article
| Open AccessOxylipins produced by Pseudomonas aeruginosa promote biofilm formation and virulence
Oxygenated fatty acids known as oxylipins play important roles in mammals, plants and fungi. Here, the authors show that oxylipins, produced by the pathogenic bacteriumPseudomonas aeruginosa, promote biofilm formation and virulence.
- Eriel Martínez
- & Javier Campos-Gómez
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Article
| Open AccessActin activates Pseudomonas aeruginosa ExoY nucleotidyl cyclase toxin and ExoY-like effector domains from MARTX toxins
The ExoY toxin is injected by Pseudomonas aeruginosainto host cells, where it is activated by an unknown host factor. Here the authors identify such factor as filamentous actin.
- Alexander Belyy
- , Dorothée Raoux-Barbot
- & Undine Mechold
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Article
| Open AccessInterfering TAL effectors of Xanthomonas oryzae neutralize R-gene-mediated plant disease resistance
The rice pathogen Xanthomonas oryzae produces TAL effectors (TALEs) that promote virulence. Here, the authors identify truncated TALEs that interfere with the function of a rice gene, Xa1, which confers resistance to all tested full-length TALEs.
- Zhiyuan Ji
- , Chonghui Ji
- & Bing Yang
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Article
| Open AccessStructure of the Neisseria meningitidis Type IV pilus
Type IV pili are present on a wide range of bacterial pathogens and mediate diverse functions. Here the authors report a high resolution crystal structure of the pilin subunit PilE, and a cryoEM reconstruction of the Type IV pilus filament from N. meningitidisthat offer insight into pilus assembly and functions.
- Subramania Kolappan
- , Mathieu Coureuil
- & Lisa Craig
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Article
| Open AccessWolbachia infections in natural Anopheles populations affect egg laying and negatively correlate with Plasmodium development
Wolbachia bacteria infect insects and could potentially be used to control populations of malaria-transmitting mosquitoes. Here, the authors provide evidence that natural Wolbachia infections affect the rate of egg laying and are associated with reduced presence of malaria parasites in Anophelesmosquitoes.
- W. Robert Shaw
- , Perrine Marcenac
- & Flaminia Catteruccia
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Article
| Open AccessA single gene of a commensal microbe affects host susceptibility to enteric infection
The interactions between gut bacteria and enteric pathogens are poorly understood. Here, Yoon et al. show that subinhibitory antibiotic treatment in a mouse model leads to overgrowth of an E. coli strain carrying a catalase-encoding gene that enhances infection with the human pathogen Vibrio cholerae.
- Mi Young Yoon
- , Kyung Bae Min
- & Sang Sun Yoon
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Article
| Open AccessGenomics reveals historic and contemporary transmission dynamics of a bacterial disease among wildlife and livestock
The role of wild elk in the spread and persistence of bovine brucellosis in the Great Yellowstone area is unclear. Here, Kamath et al. analyse the genomic sequences of 245 Brucella abortusisolates from elk, bison and cattle, supporting the idea that elk is an important reservoir and source of livestock infections.
- Pauline L. Kamath
- , Jeffrey T. Foster
- & Paul C. Cross
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Article
| Open AccessA novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria
Bacteria release outer membrane vesicles (OMVs) that play important roles in pathogenesis and intercellular interactions. Here, Roier et al. provide evidence supporting that phospholipid accumulation in the outer leaflet of the outer membrane participates in OMV formation in Gram-negative bacteria.
- Sandro Roier
- , Franz G. Zingl
- & Stefan Schild
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Article
| Open AccessCounter inhibition between leukotoxins attenuates Staphylococcus aureus virulence
Staphylococcus aureusstrains produce a family of highly related toxins that puncture the cytoplasmic membrane of susceptible cells. Here, Yoong and Torres show that the toxins can counteract each other in a cell type-dependent manner by forming inactive hybrid complexes, thus modulatingS. aureusvirulence.
- Pauline Yoong
- & Victor J. Torres
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Article
| Open AccessSialic acid catabolism drives intestinal inflammation and microbial dysbiosis in mice
Intestinal inflammation is often associated with a shift in microbiota composition but the mechanisms are unclear. Here the authors show that an increase in caecal sialidase activity occurring during intestinal inflammation promotes the expansion of Enterobacteriaceae, which can lead to exacerbated inflammatory response.
- Yen-Lin Huang
- , Christophe Chassard
- & Thierry Hennet
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Article
| Open AccessSite-specific processing of Ras and Rap1 Switch I by a MARTX toxin effector domain
V. vulnificus, a bacteria that cause life-threatening septicaemia following wound infections or tainted food consumption, utilizes MARTX toxins for toxic effector delivery. Here the authors show that the MARTX virulence factor DUF5 targets the cellular MAP kinase pathway as a Ras and Rap1 site-specific protease.
- Irena Antic
- , Marco Biancucci
- & Karla J. F. Satchell
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Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut
Gut inflammation triggers a bloom of certain resident bacteria such as E. coli that can contribute to disease. Here, Singh et al. show that a siderophore produced by E. coliinhibits the antibacterial activity of host myeloperoxidase and enhances bacterial survival in the gut of lab mice.
- Vishal Singh
- , Beng San Yeoh
- & Matam Vijay-Kumar
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| Open AccessCapturing the cloud of diversity reveals complexity and heterogeneity of MRSA carriage, infection and transmission
Populations of bacterial pathogens can be diverse within colonized individuals. Here, the authors sequence the genomes of methicillin-resistant Staphylococcus aureusisolated from staff and animal patients at a veterinary hospital and show considerable within-host diversity that can rise and fall over time.
- Gavin K. Paterson
- , Ewan M. Harrison
- & Mark A. Holmes
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MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs
Mycobacterium tuberculosis possesses several toxin–antitoxin systems of the MazEF family. Here, Tiwari et al. show that these systems contribute to stress adaptation, antibiotic tolerance and virulence.
- Prabhakar Tiwari
- , Garima Arora
- & Ramandeep Singh
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Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum
Intercellular adhesion molecules (ICAMs) participate in cellular processes such as host-pathogen interactions. Here, the authors show that ICAM-1 and ICAM-4 play roles in the invasion of macrophages and red blood cells by Mycobacterium tuberculosis and Plasmodium falciparum, respectively.
- Kuhulika Bhalla
- , Monika Chugh
- & Anand Ranganathan
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Article
| Open AccessThe Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation
Non-receptor tyrosine kinases such as Src play fundamental roles in host–pathogen interactions and phagocytosis. Here, Young et al. show that an enteropathogenic Escherichia coli(EPEC) protein, EspJ, inhibits Src activity by simultaneous amidation and ADP ribosylation of a conserved residue on the kinase.
- Joanna C. Young
- , Abigail Clements
- & Gad Frankel
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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