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| Open AccessA commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response
Faecal microbiome transplant has been shown to be able to reduce Clostridioides difficile infection. Here the authors show that an intestinal commensal protozoan reduces C. difficile infection by inhibiting neutrophil recruitment and affecting arginine-ornithine metabolism.
- Huan Yang
- , Xiaoxiao Wu
- & Bing Gu
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Article
| Open AccessNonpathogenic Pseudomonas syringae derivatives and its metabolites trigger the plant “cry for help” response to assemble disease suppressing and growth promoting rhizomicrobiome
Upon pathogen attack, plants can trigger the “cry for help” response and assemble beneficial rhizobacteria. Here, the authors use nonpathogenic Pseudomonas syringae DC3000 derivatives to elicit a similar “cry for help” response as the wild-type pathogenic DC3000 in Arabidopsis.
- Yunpeng Liu
- , Huihui Zhang
- & Ruifu Zhang
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Article
| Open AccessImmune signature of Chlamydia vaccine CTH522/CAF®01 translates from mouse-to-human and induces durable protection in mice
Authors present a comparative immunological characterisation of Chlamydia vaccine, CTH522/CAF®01, in mice and humans. Findings suggest the mouse to be a good predictor of human immunity to the Chlamydia vaccine CTH522/CAF®01, and long-lasting protection in the mouse further supports the development of this promising vaccine candidate.
- Anja W. Olsen
- , Ida Rosenkrands
- & Frank Follmann
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| Open AccessCommensal lifestyle regulated by a negative feedback loop between Arabidopsis ROS and the bacterial T2SS
The plant immune output reactive oxygen species tames a detrimental bacterial commensal from native microbiota by suppressing a bacterial secretion system, allowing the co-existence and turning it into a beneficial bacterium to the host.
- Frederickson Entila
- , Xiaowei Han
- & Kenichi Tsuda
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Article
| Open AccessGenomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci
By combining genome sequencing and antibody binding (to all common pneumococcal proteins) data, Croucher et al. present a high-resolution analysis of the emergence of immune responses in children that can protect against pneumonia.
- Nicholas J. Croucher
- , Joseph J. Campo
- & David Goldblatt
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Article
| Open AccessGeometric constraint-triggered collagen expression mediates bacterial-host adhesion
Cells in the body live in geometrically constrained microenvironments. Here, Feng at al report that these constraints induce collagen IV expression which is responsible for location dependent bacterial adhesion.
- Yuting Feng
- , Shuyi Wang
- & Jianyong Huang
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Article
| Open AccessFiber supplementation protects from antibiotic-induced gut microbiome dysbiosis by modulating gut redox potential
Here, the authors show that fiber supplementation protects from antibiotic-induced gut microbiome damage by reducing the abundance of aerobic bacteria as well as metabolic pathways associated with oxidative metabolism.
- Swathi Penumutchu
- , Benjamin J. Korry
- & Peter Belenky
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Article
| Open AccessGenetic strategies for sex-biased persistence of gut microbes across human life
Here, via analyses of shotgun metagenomic sequencing data of more than 12,000 fecal microbiomes from healthy individuals, the authors reveal the presence of microbiome genetic traits involved in host mucin metabolism, supporting colonization and persistence of specific bacterial strains preferentially in the intestinal environment of women compared to men.
- Chiara Tarracchini
- , Giulia Alessandri
- & Marco Ventura
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Comment
| Open AccessFerroptosis hijacking by Mycobacterium tuberculosis
A recent study from Nature Communications reveals that Mycobacterium tuberculosis can hijack epigenetic machinery in host cells and induce host cell ferroptosis, which promotes pathogen pathogenicity and spread. These findings also suggest new therapeutic strategies to treat tuberculosis.
- Boyi Gan
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Article
| Open AccessMicroscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature
Staphylococcus aureus is increasingly recognized as a facultative intracellular pathogen, but it is unclear whether the intracellular lifestyle is a general feature or is restricted to some isolates. Here, Rodrigues Lopes et al. profile the interaction of 191 clinical isolates with four host cell types over time, showing that almost all isolates are internalized and that a large fraction replicate and persist within host cells.
- Ines Rodrigues Lopes
- , Laura Maria Alcantara
- & Ana Eulalio
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Article
| Open AccessAutoinducer-2 and bile salts induce c-di-GMP synthesis to repress the T3SS via a T3SS chaperone
Cyclic-di-GMP transduces extracellular stimuli into intracellular responses to modulate important biological processes. Here, the authors show that AI-2 and bile salts induce cyclic-di-GMP synthesis via YeaJ and YedQ, respectively, to repress the T3SS via a cyclic-di-GMP-responsive T3SS chaperone.
- Shuyu Li
- , Hengxi Sun
- & Lei Zhang
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Article
| Open AccessA single transcription factor facilitates an insect host combating Bacillus thuringiensis infection while maintaining fitness
Plutella xylostella endures Bt toxins with no performance costs. This study reveals how, depending on the presence of the toxin, this insect modifies MAPK phosphorylation to modulate the transcription factor FTZ-F1 binding, to up- or down- regulate Bt receptors or non-receptor (resistant) paralogs.
- Zhaojiang Guo
- , Le Guo
- & Youjun Zhang
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Article
| Open AccessCombined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy
IgE is a critical component of the allergic response and therapeutic targeting can alleviate symptomology. Here the authors propose the combined use of Bifidobacterium longum and a FcεRIα extracellular domain linked to a IgD/IgG4 hybrid Fc domain fusion protein called IgETRAP and show reduction of mast cell and IgE levels in models of food allergy.
- Seong Beom An
- , Bo-Gie Yang
- & Myoung Ho Jang
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Article
| Open AccessBacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
Here, Diot et al. use the nematode Caenorhabditis elegans as a model to identify off-target toxicity mechanisms for tamoxifen, and find that these include fatty acid metabolism and cell death, which can be modulated by different bacterial species.
- Cédric Diot
- , Aurian P. García-González
- & Albertha J. M. Walhout
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Article
| Open AccessOral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota
Here, the authors inversely associate Blautia wexlerae with obesity and type 2 diabetes mellitus in humans and further show that administration of B. wexlerae to mice decrease both high-fat diet–induced obesity and diabetes via modulating gut microbial metabolism.
- Koji Hosomi
- , Mayu Saito
- & Jun Kunisawa
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Article
| Open AccessDietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles
Secretory IgA plays vital roles interfacing between the host immune system and the resident microbiota at the mucosal surface. Here the authors explore the effect of dietary protein on the production of secretory IgA, driven by the production of extracellular vesicles by the intestinal microbiota.
- Jian Tan
- , Duan Ni
- & Laurence Macia
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Article
| Open AccessAirway Prevotella promote TLR2-dependent neutrophil activation and rapid clearance of Streptococcus pneumoniae from the lung
How the airway microbiome protects against bacterial pneumonia remains unclear. Here, the authors identify airway bacterial species that activate the immune system to facilitate rapid clearance of the pathogen Streptococcus pneumoniae from the lung.
- Kadi J. Horn
- , Melissa A. Schopper
- & Sarah E. Clark
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Article
| Open AccessEarly alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains
Halting tuberculosis transmission is crucial to TB elimination. Here the authors implicate IL-1R dependent T cell priming as the underlying mechanism determining variability in transmission of Mycobacterium tuberculosis strains.
- Arianne Lovey
- , Sheetal Verma
- & Padmini Salgame
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Article
| Open AccessCitrus Huanglongbing is a pathogen-triggered immune disease that can be mitigated with antioxidants and gibberellin
Huanglongbing is a devastating disease of citrus, caused by phloem-colonizing bacteria. Here, the authors present evidence that the disease is the result of an exacerbated immune response to the infection, including production of reactive oxygen species, and that antioxidants and a growth-promoting hormone can mitigate disease symptoms.
- Wenxiu Ma
- , Zhiqian Pang
- & Nian Wang
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Article
| Open AccessFree fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection
Hematopoietic stem cells (HSCs) rapidly expand upon infection, switching their metabolic profile to increase OXPHOS. Here, the authors show in mouse models that infection promotes uptake of long-chain free fatty acids via CD36, which is required for a protective response.
- Jayna J. Mistry
- , Charlotte Hellmich
- & Stuart A. Rushworth
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Article
| Open AccessPsychological stress impairs IL22-driven protective gut mucosal immunity against colonising pathobionts
Altered gut microbiome and exacerbation of symptoms at times of psychological stress are feature characteristics of Crohn’s disease. Here authors show in a mouse model that psychological stress impairs IL-22-dependent protective immunity of the ileal mucosa, which allows invasive bacteria to colonise the gut.
- Christopher R. Shaler
- , Alexandra A. Parco
- & Brian K. Coombes
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Article
| Open AccessChlamydia evasion of neutrophil host defense results in NLRP3 dependent myeloid-mediated sterile inflammation through the purinergic P2X7 receptor
Myeloid cells are implicated in the innate immune and inflammatory response during infection with Chlamydia trachomatis. Here the authors show the evasion of the neutrophil response to infection and concomitant induction of sterile immunity via the purinergic P2X7 receptor.
- Chunfu Yang
- , Lei Lei
- & Harlan D. Caldwell
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Article
| Open AccessMechanistic insight into bacterial entrapment by septin cage reconstitution
Septins are cytoskeletal proteins that assemble into complexes and contribute to immunity by entrapping intracellular bacteria in cage-like structures. Here, Lobato-Márquez et al. reconstitute septin cages in vitro using purified recombinant complexes, and study how these recognize bacterial cells and assemble as filaments on their surface.
- Damián Lobato-Márquez
- , Jingwei Xu
- & Serge Mostowy
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Article
| Open AccessTLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection
Innate immune cells respond to a number of environmental cues including TLR signalling. Here the authors implicate mechanical sensor Piezo1 in the TLR4 mediated host response to bacterial infection and implicate it in the enhancement of macrophage mediated host response.
- Jing Geng
- , Yiran Shi
- & Dawang Zhou
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Article
| Open AccessAbiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients
Abiraterone acetate (AA) is indicated for the treatment of patients with metastatic castrate-resistant prostate cancer. Here, the authors show that, in prostate cancer patients, orally administered AA remodels the gut microbiome and promotes the enrichment of the commensal bacterium Akkermansia muciniphila at the expense of androgen-utilizing Corynebacterium species.
- Brendan A. Daisley
- , Ryan M. Chanyi
- & Jeremy P. Burton
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Article
| 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 AccessCross-serotype protection against group A Streptococcal infections induced by immunization with SPy_2191
A high number of serotypes makes vaccine development to group A Streptococcus (GAS) difficult. Here, the authors use a reverse vaccinology approach and identify SPy_2191 as conserved surface protein that inhibits GAS adhesion and invasion and induces cross-protective immunity in mice.
- Pooja Sanduja
- , Manish Gupta
- & Atul Kumar Johri
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Article
| Open AccessDual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
Studying emerging pathogens is often challenging due to the lack of information. Here the authors show that dual RNA-seq, profiling the host and pathogen transcriptome simultaneously, helps uncovering the biology of Orientia tsutsugamushi, a major cause of febrile illness in South-East Asia, and its interaction with the host.
- Bozena Mika-Gospodorz
- , Suparat Giengkam
- & Jeanne Salje
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Article
| Open AccessErythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration
Gut microbiota and their metabolites regulate homeostasis of the intestine, but their effects on intestine development are unclear. Here the authors use RNAseq and germ free mice to show that intestinal microbiota promote the expression of Erdr1, which increases Lgr5+ intestinal stem cell number and activity.
- Hirohito Abo
- , Benoit Chassaing
- & Timothy L. Denning
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Article
| Open AccessAfrican-centric TP53 variant increases iron accumulation and bacterial pathogenesis but improves response to malaria toxin
A polymorphism in human TP53 (P47S) that predominantly exists in individuals of African descent affects ferroptosis. Here, the authors show that this results in iron accumulation in macrophages leading to more productive infection by intracellular bacteria but improved anti-inflammatory response to the malarial toxin hemozoin.
- Kumar Sachin Singh
- , Julia I-Ju Leu
- & Farokh Dotiwala
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Article
| Open AccessThe in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection
ISG15 is a ubiquitin-like modifier that can be upregulated in response to bacterial infections. Here, the authors use proteomics to identify endogenous ISGylation substrates in the liver of Listeria monocytogenes infected mice and show that ISGylation alters basal and infection-induced autophagy.
- Yifeng Zhang
- , Fabien Thery
- & Lilliana Radoshevich
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Article
| Open AccessBacterial variability in the mammalian gut captured by a single-cell synthetic oscillator
Synthetic gene oscillators can be used to control timed function and periodic expression of genes. Here the authors demonstrate in vivo implementation in the mammalian gut that can keep time over several days.
- David T. Riglar
- , David L. Richmond
- & Pamela A. Silver
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Article
| Open AccessInterleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction
IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.
- Eirini Giannoudaki
- , Yasmina E. Hernandez-Santana
- & Patrick T. Walsh
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| 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 AccessBacteria evoke alarm behaviour in zebrafish
When injured, fish release an alarm substance produced by club cells in the skin that elicits fear in members of their shoal. Here, the authors show that mucus and bacteria are transported from the external surface into club cells, and bacterial components elicit alarm behaviour, acting in concert with a substance from fish.
- Joanne Shu Ming Chia
- , Elena S. Wall
- & Suresh Jesuthasan
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Article
| Open AccessHigh-throughput screen reveals sRNAs regulating crRNA biogenesis by targeting CRISPR leader to repress Rho termination
Small non-coding RNAs (sRNA) regulate bacterial functions by finding nucleic acids and proteins. Here the authors identify PhrS sRNA in Pseudomonas as a positive regulator of CRISPR, and show PhrS acts by binding to CRISPR leader, thereby preventing Rho-mediated transcription termination and promoting anti-bacteriophage immunity.
- Ping Lin
- , Qinqin Pu
- & Min Wu
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Article
| Open AccessPredicting bacterial infection outcomes using single cell RNA-sequencing analysis of human immune cells
Complex interactions between different host immune cell types can determine the outcome of pathogen infections. Here, Avraham and colleagues present a deconvolution algorithm that uses single-cell RNA and bulk RNA sequencing measurements of pathogen-infected cells to predict disease risk outcomes.
- Noa Bossel Ben-Moshe
- , Shelly Hen-Avivi
- & Roi Avraham
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Article
| Open AccessActive thrombin produced by the intestinal epithelium controls mucosal biofilms
The roles played by thrombin in the human intestinal mucosa are unclear. Here, the authors show that the commensal microbiota modulates epithelial production of active thrombin, which controls biofilm growth and contributes to protection of the mucosa from bacterial invasion.
- Jean-Paul Motta
- , Alexandre Denadai-Souza
- & Nathalie Vergnolle
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Article
| Open AccessA quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies
Characterizing host-pathogen protein interactions can help elucidate the molecular basis of bacterial infections. Here, the authors use an integrative proteomics approach to generate a quantitative map of protein interactions between Streptococcus pyogenes and human saliva and plasma.
- Lotta Happonen
- , Simon Hauri
- & Johan Malmström
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Article
| Open AccessIL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection
Here, Frisbee et al. show that hypervirulent Clostridium difficile induces IL-33 expression in the gut and IL-33 reduces mortality and morbidity via group 2 innate lymphoid cells. Furthermore, serum levels of the soluble IL-33 decoy receptor, sST2, are associated with enhanced disease severity in human C. difficile patients.
- Alyse L. Frisbee
- , Mahmoud M. Saleh
- & William A. Petri Jr.
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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 AccessCorticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition
Corticosteroids are host-directed drugs that enhance survival of tuberculosis patients through unclear mechanisms. Here, Gräb et al. show that corticosteroids inhibit necrotic death of cells infected with Mycobacterium tuberculosis by facilitating MKP-1-dependent dephosphorylation of p38 MAPK.
- Jessica Gräb
- , Isabelle Suárez
- & Jan Rybniker
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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 AccessMrp1 is involved in lipid presentation and iNKT cell activation by Streptococcus pneumoniae
The CD1d pathway present lipid antigens resulting in the activation of iNKT cells but the complete pathway remains to be fully elucidated. Here, Chandra et al. use an siRNA screen and identify Mrp1 as crucial for CD1d lipid presentation and activation of iNKT in the context of Streptococcus pneumoniae infection.
- Shilpi Chandra
- , James Gray
- & Mitchell Kronenberg
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Article
| 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 AccessVibrio vulnificus quorum-sensing molecule cyclo(Phe-Pro) inhibits RIG-I-mediated antiviral innate immunity
Quorum sensing signaling molecules are known to be critical determinants in bacterial pathogenesis. Here the authors show the quorum sensing molecule cFP from Vibrio vulnificus inhibits the RIG-I mediated antiviral interferon response and enhances susceptibility to viral infection.
- Wooseong Lee
- , Seung-Hoon Lee
- & Jong-Won Oh
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Article
| Open AccessPerturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells
Wolbachia infection of mosquitoes can block dengue virus infection and is tested in field trials, but the mechanism of action is unclear. Using proteomics, Geoghegan et al. here identify effects of Wolbachia on cholesterol homeostasis and dengue virus replication in Aedes aegypti.
- Vincent Geoghegan
- , Kirsty Stainton
- & Steven P. Sinkins
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Article
| Open AccessExploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis
In vitro models to study the role of host genetics in the response to chlamydial infection are limited. Here, Yeung et al. show that macrophages derived from human induced pluripotent stem cells (which can be genetically manipulated) support chlamydial infection and can be used for this purpose.
- Amy T. Y. Yeung
- , Christine Hale
- & Robert E. W. Hancock
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Article
| Open AccessHost-inherent variability influences the transcriptional response of Staphylococcus aureus during in vivo infection
Drugs inhibiting virulence factors of bacterial pathogens are under development. Here, Thänertet al. analyse the transcriptomes of host and pathogen during Staphylococcus aureusinfection of two mouse strains, and show that virulence determinants are differentially expressed in different mouse strains.
- Robert Thänert
- , Oliver Goldmann
- & Eva Medina