当前位置： SCI文献检索 > Nature Microbiology期刊下所有文献 > Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis.

Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis.

Abstract：

:Clostridium difficile infection (CDI) is mediated by two major exotoxins, toxin A (TcdA) and toxin B (TcdB), that damage the colonic epithelial barrier and induce inflammatory responses. The function of the colonic vascular barrier during CDI has been relatively understudied. Here we report increased colonic vascular permeability in CDI mice and elevated vascular endothelial growth factor A (VEGF-A), which was induced in vivo by infection with TcdA- and/or TcdB-producing C. difficile strains but not with a TcdA-TcdB- isogenic mutant. TcdA or TcdB also induced the expression of VEGF-A in human colonic mucosal biopsies. Hypoxia-inducible factor signalling appeared to mediate toxin-induced VEGF production in colonocytes, which can further stimulate human intestinal microvascular endothelial cells. Both neutralization of VEGF-A and inhibition of its signalling pathway attenuated CDI in vivo. Compared to healthy controls, CDI patients had significantly higher serum VEGF-A that subsequently decreased after treatment. Our findings indicate critical roles for toxin-induced VEGF-A and colonic vascular permeability in CDI pathogenesis and may also point to the pathophysiological significance of the gut vascular barrier in response to virulence factors of enteric pathogens. As an alternative to pathogen-targeted therapy, this study may enable new host-directed therapeutic approaches for severe, refractory CDI.

journal_name

Nat Microbiol

journal_title

Nature microbiology

authors

Huang J,Kelly CP,Bakirtzi K,Villafuerte Gálvez JA,Lyras D,Mileto SJ,Larcombe S,Xu H,Yang X,Shields KS,Zhu W,Zhang Y,Goldsmith JD,Patel IJ,Hansen J,Huang M,Yla-Herttuala S,Moss AC,Paredes-Sabja D,Pothoulakis C,Shah

doi

10.1038/s41564-018-0300-x

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

269-279

issue

2

issn

2058-5276

pii

10.1038/s41564-018-0300-x

journal_volume

4

pub_type

杂志文章

相关文献

Nature Microbiology文献大全
  • A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation.

    abstract：:Pathogenic bacteria are armed with potent effector proteins that subvert host signalling processes during infection1. The activities of bacterial effectors and their associated roles within the host cell are often poorly understood, particularly for Chlamydia trachomatis2, a World Health Organization designated neglec...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-018-0271-y

    authors： Pruneda JN,Bastidas RJ,Bertsoulaki E,Swatek KN,Santhanam B,Clague MJ,Valdivia RH,Urbé S,Komander D

    更新日期：2018-12-01 00:00:00

  • Carcinogenesis and therapeutics: the microbiota perspective.

    abstract：:Cancer arises from the acquisition of multiple genetic and epigenetic changes in host cells over the span of many years, promoting oncogenic traits and carcinogenesis. Most cancers develop following random somatic alterations of key oncogenic genes, which are favoured by a number of risk factors, including lifestyle, ...

    journal_title：Nature microbiology

    pub_type： 杂志文章,评审

    doi：10.1038/nmicrobiol.2017.8

    authors： Tsilimigras MC,Fodor A,Jobin C

    更新日期：2017-02-22 00:00:00

  • Epstein-Barr virus ncRNA from a nasopharyngeal carcinoma induces an inflammatory response that promotes virus production.

    abstract：:The Epstein-Barr virus M81 strain, isolated from a nasopharyngeal carcinoma, induces potent spontaneous virus production in infected B cells. We found that the M81 non-coding Epstein-Barr-encoded RNA EBER2, which carries polymorphisms that are mainly restricted to viruses found in endemic nasopharyngeal carcinomas, ma...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-019-0546-y

    authors： Li Z,Tsai MH,Shumilov A,Baccianti F,Tsao SW,Poirey R,Delecluse HJ

    更新日期：2019-12-01 00:00:00

  • Bacillus subtilis cell diameter is determined by the opposing actions of two distinct cell wall synthetic systems.

    abstract：:Rod-shaped bacteria grow by adding material into their cell wall via the action of two spatially distinct enzymatic systems: the Rod complex moves around the cell circumference, whereas class A penicillin-binding proteins (aPBPs) do not. To understand how the combined action of these two systems defines bacterial dime...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-019-0439-0

    authors： Dion MF,Kapoor M,Sun Y,Wilson S,Ryan J,Vigouroux A,van Teeffelen S,Oldenbourg R,Garner EC

    更新日期：2019-08-01 00:00:00

  • VacA generates a protective intracellular reservoir for Helicobacter pylori that is eliminated by activation of the lysosomal calcium channel TRPML1.

    abstract：:Helicobacter pylori infection is a proven carcinogen for gastric cancer. Its virulence factor vacuolating cytotoxin A (VacA) promotes more severe disease and gastric colonization. VacA, by an unknown mechanism, usurps lysosomal and autophagy pathways to generate a protected reservoir for H. pylori that confers bacteri...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-019-0441-6

    authors： Capurro MI,Greenfield LK,Prashar A,Xia S,Abdullah M,Wong H,Zhong XZ,Bertaux-Skeirik N,Chakrabarti J,Siddiqui I,O'Brien C,Dong X,Robinson L,Peek RM Jr,Philpott DJ,Zavros Y,Helmrath M,Jones NL

    更新日期：2019-08-01 00:00:00

  • Methods for phylogenetic analysis of microbiome data.

    abstract：:How does knowing the evolutionary history of microorganisms affect our analysis of microbiological datasets? Depending on the research question, the common ancestry of microorganisms can be a source of confounding variation, or a scaffolding used for inference. For example, when performing regression on traits, common...

    journal_title：Nature microbiology

    pub_type： 杂志文章,评审

    doi：10.1038/s41564-018-0156-0

    authors： Washburne AD,Morton JT,Sanders J,McDonald D,Zhu Q,Oliverio AM,Knight R

    更新日期：2018-06-01 00:00:00

  • Murine colitis reveals a disease-associated bacteriophage community.

    abstract：:The dysregulation of intestinal microbial communities is associated with inflammatory bowel diseases (IBD). Studies aimed at understanding the contribution of the microbiota to inflammatory diseases have primarily focused on bacteria, yet the intestine harbours a viral component dominated by prokaryotic viruses known ...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-018-0210-y

    authors： Duerkop BA,Kleiner M,Paez-Espino D,Zhu W,Bushnell B,Hassell B,Winter SE,Kyrpides NC,Hooper LV

    更新日期：2018-09-01 00:00:00

  • Professional titles matter.

    abstract：: ...

    journal_title：Nature microbiology

    pub_type： 社论

    doi：10.1038/s41564-018-0320-6

    authors：

    更新日期：2018-12-01 00:00:00

  • Excess of non-conservative amino acid changes in marine bacterioplankton lineages with reduced genomes.

    abstract：:Surface ocean waters are dominated by planktonic bacterial lineages with highly reduced genomes. The best examples are the cyanobacterial genus Prochlorococcus, the alphaproteobacterial clade SAR11 and the gammaproteobacterial clade SAR86, which together represent over 50% of the cells in surface oceans. Several studi...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/nmicrobiol.2017.91

    authors： Luo H,Huang Y,Stepanauskas R,Tang J

    更新日期：2017-06-12 00:00:00

  • Crystal structure of Clostridium difficile toxin A.

    abstract：:Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Disease is mediated by the actions of two toxins, TcdA and TcdB, which cause the diarrhoea, as well as inflammation and necrosis within the colon. The toxins are large (308 and 270 kDa, respectively), homo...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/nmicrobiol.2015.2

    authors： Chumbler NM,Rutherford SA,Zhang Z,Farrow MA,Lisher JP,Farquhar E,Giedroc DP,Spiller BW,Melnyk RA,Lacy DB

    更新日期：2016-01-11 00:00:00

  • Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2.

    abstract：:Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease-a disease endemic especially in the Asia-Pacific region1. Scavenger receptor class B member 2 (SCARB2) is the major receptor of EV71, as well as several other enteroviruses responsible for hand, foot and mouth disease, and plays a key role in cell...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-018-0319-z

    authors： Zhou D,Zhao Y,Kotecha A,Fry EE,Kelly JT,Wang X,Rao Z,Rowlands DJ,Ren J,Stuart DI

    更新日期：2019-03-01 00:00:00

  • A natural toroidal microswimmer with a rotary eukaryotic flagellum.

    abstract：:We describe Idionectes vortex gen. nov., sp. nov., a unicellular microeukaryote that swims by continuous inversion of its surface, similar to a vortex ring. This previously unreported mode of motility approximates a hypothetical concept called the 'toroidal swimmer', in which a doughnut-shaped object rotates around it...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-019-0478-6

    authors： Hess S,Eme L,Roger AJ,Simpson AGB

    更新日期：2019-10-01 00:00:00

  • Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.

    abstract：:Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and on...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-018-0230-7

    authors： Lee JYH,Monk IR,Gonçalves da Silva A,Seemann T,Chua KYL,Kearns A,Hill R,Woodford N,Bartels MD,Strommenger B,Laurent F,Dodémont M,Deplano A,Patel R,Larsen AR,Korman TM,Stinear TP,Howden BP

    更新日期：2018-10-01 00:00:00

  • Defining the human gut host-phage network through single-cell viral tagging.

    abstract：:Viral discovery is accelerating at an unprecedented rate due to continuing advances in culture-independent sequence-based analyses. One important facet of this discovery is identification of the hosts of these recently characterized uncultured viruses. To this end, we have adapted the viral tagging approach, which byp...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-019-0526-2

    authors： Džunková M,Low SJ,Daly JN,Deng L,Rinke C,Hugenholtz P

    更新日期：2019-12-01 00:00:00

  • Structure of human Aichi virus and implications for receptor binding.

    abstract：:Aichi virus (AiV), an unusual and poorly characterized picornavirus, classified in the genus Kobuvirus, can cause severe gastroenteritis and deaths in children below the age of five years, especially in developing countries1,2. The seroprevalence of AiV is approximately 60% in children under the age of ten years and r...

    journal_title：Nature microbiology

    pub_type： 信件

    doi：10.1038/nmicrobiol.2016.150

    authors： Zhu L,Wang X,Ren J,Kotecha A,Walter TS,Yuan S,Yamashita T,Tuthill TJ,Fry EE,Rao Z,Stuart DI

    更新日期：2016-09-05 00:00:00

  • Phosphatidic acid governs natural egress in Toxoplasma gondii via a guanylate cyclase receptor platform.

    abstract：:Toxoplasma gondii establishes a lifelong chronic infection in humans and animals1. Host cell entry and egress are key steps in the lytic cycle of this obligate intracellular parasite, ensuring its survival and dissemination. Egress is temporally orchestrated, underpinned by the exocytosis of secretory organelles calle...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-018-0339-8

    authors： Bisio H,Lunghi M,Brochet M,Soldati-Favre D

    更新日期：2019-03-01 00:00:00

  • Primate immunodeficiency virus proteins Vpx and Vpr counteract transcriptional repression of proviruses by the HUSH complex.

    abstract：:Host factors that silence provirus transcription in CD4+ memory T cells help HIV-1 escape eradication by the host immune system and by antiviral drugs1. These same factors, however, must be overcome for HIV-1 to propagate. Here we show that Vpx and Vpr encoded by diverse primate immunodeficiency viruses activate provi...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-018-0256-x

    authors： Yurkovetskiy L,Guney MH,Kim K,Goh SL,McCauley S,Dauphin A,Diehl WE,Luban J

    更新日期：2018-12-01 00:00:00

  • The anti-inflammatory drug mesalamine targets bacterial polyphosphate accumulation.

    abstract：:Mesalamine serves as the gold standard in treating ulcerative colitis. However, its precise mechanism(s) of action remains unclear. Here, we show that mesalamine treatment rapidly decreases polyphosphate levels in diverse bacteria, including members of the human gut microbiome. This decrease sensitizes bacteria toward...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/nmicrobiol.2016.267

    authors： Dahl JU,Gray MJ,Bazopoulou D,Beaufay F,Lempart J,Koenigsknecht MJ,Wang Y,Baker JR,Hasler WL,Young VB,Sun D,Jakob U

    更新日期：2017-01-23 00:00:00

  • Exaggerated headline shock.

    abstract：: ...

    journal_title：Nature microbiology

    pub_type： 社论

    doi：10.1038/s41564-019-0408-7

    authors：

    更新日期：2019-03-01 00:00:00

  • Chance and pleiotropy dominate genetic diversity in complex bacterial environments.

    abstract：:How does environmental complexity affect the evolution of single genes? Here, we measured the effects of a set of Bacillus subtilis glutamate dehydrogenase mutants across 19 different environments-from phenotypically homogeneous single-cell populations in liquid media to heterogeneous biofilms, plant roots and soil po...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-019-0412-y

    authors： Noda-García L,Davidi D,Korenblum E,Elazar A,Putintseva E,Aharoni A,Tawfik DS

    更新日期：2019-07-01 00:00:00

  • A nonlinear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance.

    abstract：:Balancing access to antibiotics with the control of antibiotic resistance is a global public health priority. At present, antibiotic stewardship is informed by a 'use it and lose it' principle, in which antibiotic use by the population is linearly related to resistance rates. However, theoretical and mathematical mode...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-019-0410-0

    authors： López-Lozano JM,Lawes T,Nebot C,Beyaert A,Bertrand X,Hocquet D,Aldeyab M,Scott M,Conlon-Bingham G,Farren D,Kardos G,Fésűs A,Rodríguez-Baño J,Retamar P,Gonzalo-Jiménez N,Gould IM,THRESHOLDS study group.

    更新日期：2019-07-01 00:00:00

  • Broad-spectrum anti-CRISPR proteins facilitate horizontal gene transfer.

    abstract：:CRISPR-Cas adaptive immune systems protect bacteria and archaea against their invading genetic parasites, including bacteriophages/viruses and plasmids. In response to this immunity, many phages have anti-CRISPR (Acr) proteins that inhibit CRISPR-Cas targeting. To date, anti-CRISPR genes have primarily been discovered...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-020-0692-2

    authors： Mahendra C,Christie KA,Osuna BA,Pinilla-Redondo R,Kleinstiver BP,Bondy-Denomy J

    更新日期：2020-04-01 00:00:00

  • AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling.

    abstract：:Zika virus (ZIKV) is associated with neonatal microcephaly and Guillain-Barré syndrome1,2. While progress has been made in understanding the causal link between ZIKV infection and microcephaly3-9, the life cycle and pathogenesis of ZIKV are less well understood. In particular, there are conflicting reports on the role...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-017-0092-4

    authors： Chen J,Yang YF,Yang Y,Zou P,Chen J,He Y,Shui SL,Cui YR,Bai R,Liang YJ,Hu Y,Jiang B,Lu L,Zhang X,Liu J,Xu J

    更新日期：2018-03-01 00:00:00

  • Spermine-mediated tight sealing of the Magnaporthe oryzae appressorial pore-rice leaf surface interface.

    abstract：:Cellular adhesion mediates many important plant-microbe interactions. In the devastating blast fungus Magnaporthe oryzae1, powerful glycoprotein-rich mucilage adhesives2 cement melanized and pressurized dome-shaped infection cells-appressoria-to host rice leaf surfaces. Enormous internal turgor pressure is directed on...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-020-0786-x

    authors： Rocha RO,Elowsky C,Pham NTT,Wilson RA

    更新日期：2020-12-01 00:00:00

  • Pneumococcal quorum sensing drives an asymmetric owner-intruder competitive strategy during carriage via the competence regulon.

    abstract：:Competition among microorganisms is a key determinant of successful host colonization and persistence. For Streptococcus pneumoniae, lower than predicted rates of co-colonizing strains suggest a competitive advantage for resident bacteria over newcomers. In light of evolutionary theory, we hypothesized that S. pneumon...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-018-0314-4

    authors： Shen P,Lees JA,Bee GCW,Brown SP,Weiser JN

    更新日期：2019-01-01 00:00:00

  • Publisher Correction: Collapse of genetic division of labour and evolution of autonomy in pellicle biofilms.

    abstract：:In the version of this Article originally published, author Carolina Falcón Garcia's name was coded wrongly, resulting in it being incorrect when exported to citation databases. This has now been corrected, though no visible changes will be apparent. ...

    journal_title：Nature microbiology

    pub_type： 已发布勘误

    doi：10.1038/s41564-018-0350-0

    authors： Dragoš A,Martin M,Garcia CF,Kricks L,Pausch P,Heimerl T,Bálint B,Maróti G,Bange G,López D,Lieleg O,Kovács ÁT

    更新日期：2019-02-01 00:00:00

  • Evolution of host adaptation in the Salmonella typhoid toxin.

    abstract：:The evolution of virulence traits is central for the emergence or re-emergence of microbial pathogens and for their adaptation to a specific host 1-5 . Typhoid toxin is an essential virulence factor of the human-adapted bacterial pathogen Salmonella Typhi 6,7 , the cause of typhoid fever in humans 8-12 . Typhoid toxin...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-017-0033-2

    authors： Gao X,Deng L,Stack G,Yu H,Chen X,Naito-Matsui Y,Varki A,Galán JE

    更新日期：2017-12-01 00:00:00

  • Roles of bacteriophages, plasmids and CRISPR immunity in microbial community dynamics revealed using time-series integrated meta-omics.

    abstract：:Viruses and plasmids (invasive mobile genetic elements (iMGEs)) have important roles in shaping microbial communities, but their dynamic interactions with CRISPR-based immunity remain unresolved. We analysed generation-resolved iMGE-host dynamics spanning one and a half years in a microbial consortium from a biologica...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-020-00794-8

    authors： Martínez Arbas S,Narayanasamy S,Herold M,Lebrun LA,Hoopmann MR,Li S,Lam TJ,Kunath BJ,Hicks ND,Liu CM,Price LB,Laczny CC,Gillece JD,Schupp JM,Keim PS,Moritz RL,Faust K,Tang H,Ye Y,Skupin A,May P,Muller EEL,Wilm

    更新日期：2021-01-01 00:00:00

  • A surface endogalactanase in Bacteroides thetaiotaomicron confers keystone status for arabinogalactan degradation.

    abstract：:Glycans are major nutrients for the human gut microbiota (HGM). Arabinogalactan proteins (AGPs) comprise a heterogenous group of plant glycans in which a β1,3-galactan backbone and β1,6-galactan side chains are conserved. Diversity is provided by the variable nature of the sugars that decorate the galactans. The mecha...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-018-0258-8

    authors： Cartmell A,Muñoz-Muñoz J,Briggs JA,Ndeh DA,Lowe EC,Baslé A,Terrapon N,Stott K,Heunis T,Gray J,Yu L,Dupree P,Fernandes PZ,Shah S,Williams SJ,Labourel A,Trost M,Henrissat B,Gilbert HJ

    更新日期：2018-11-01 00:00:00

  • Environmental drivers of a microbial genomic transition zone in the ocean's interior.

    abstract：:The core properties of microbial genomes, including GC content and genome size, are known to vary widely among different bacteria and archaea 1,2 . Several hypotheses have been proposed to explain this genomic variability, but the fundamental drivers that shape bacterial and archaeal genomic properties remain uncertai...

    journal_title：Nature microbiology

    pub_type： 杂志文章

    doi：10.1038/s41564-017-0008-3

    authors： Mende DR,Bryant JA,Aylward FO,Eppley JM,Nielsen T,Karl DM,DeLong EF

    更新日期：2017-10-01 00:00:00