Abstract:
:Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and its frequent complication with ulcerative colitis highlights the pathogenic role of epithelial barrier dysfunction. Intestinal barrier dysfunction has been implicated in the pathogenesis of PSC, yet its underlying mechanism remains unknown. Here, we identify Klebsiella pneumonia in the microbiota of patients with PSC and demonstrate that K. pneumoniae disrupts the epithelial barrier to initiate bacterial translocation and liver inflammatory responses. Gnotobiotic mice inoculated with PSC-derived microbiota exhibited T helper 17 (TH17) cell responses in the liver and increased susceptibility to hepatobiliary injuries. Bacterial culture of mesenteric lymph nodes in these mice isolated K. pneumoniae, Proteus mirabilis and Enterococcus gallinarum, which were prevalently detected in patients with PSC. A bacterial-organoid co-culture system visualized the epithelial-damaging effect of PSC-derived K. pneumoniae that was associated with bacterial translocation and susceptibility to TH17-mediated hepatobiliary injuries. We also show that antibiotic treatment ameliorated the TH17 immune response induced by PSC-derived microbiota. These results highlight the role of pathobionts in intestinal barrier dysfunction and liver inflammation, providing insights into therapeutic strategies for PSC.
journal_name
Nat Microbioljournal_title
Nature microbiologyauthors
Nakamoto N,Sasaki N,Aoki R,Miyamoto K,Suda W,Teratani T,Suzuki T,Koda Y,Chu PS,Taniki N,Yamaguchi A,Kanamori M,Kamada N,Hattori M,Ashida H,Sakamoto M,Atarashi K,Narushima S,Yoshimura A,Honda K,Sato T,Kanai Tdoi
10.1038/s41564-018-0333-1subject
Has Abstractpub_date
2019-03-01 00:00:00pages
492-503issue
3issn
2058-5276pii
10.1038/s41564-018-0333-1journal_volume
4pub_type
杂志文章abstract::The microbial environment influences animal physiology. However, the underlying molecular mechanisms of such functional interactions are largely undefined. Previously, we showed that during chronic undernutrition, strains of Lactobacillus plantarum, a major commensal partner of Drosophila, promote host juvenile growth...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-017-0038-x
更新日期:2017-12-01 00:00:00
abstract::The IncC family of broad-host-range plasmids enables the spread of antibiotic resistance genes among human enteric pathogens1-3. Although aspects of IncC plasmid conjugation have been well studied4-9, many roles of conjugation genes have been assigned based solely on sequence similarity. We applied hypersaturated tran...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-020-0775-0
更新日期:2020-11-01 00:00:00
abstract::A major form of transcriptional regulation in bacteria occurs through the exchange of the primary σ factor of RNA polymerase (RNAP) with an alternative extracytoplasmic function (ECF) σ factor1. ECF σ factors are generally intrinsically active and are retained in an inactive state via the sequestration into σ factor-a...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-019-0648-6
更新日期:2020-03-01 00:00:00
abstract::Zika virus is a mosquito-borne pathogen that is rapidly spreading across the Americas. Due to associations between Zika virus infection and a range of fetal maladies(1,2), the epidemic trajectory of this viral infection poses a significant concern for the nearly 15 million children born in the Americas each year. Asce...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/nmicrobiol.2016.126
更新日期:2016-07-25 00:00:00
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
更新日期:2019-08-01 00:00:00
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
更新日期:2018-03-01 00:00:00
abstract::In most Gram-negative pathogens, the hydrolysis of UDP-2,3-diacylglucosamine to generate lipid X in lipid A biosynthesis is catalysed by the membrane-associated enzyme LpxH. We report the crystal structure of LpxH in complex with its product, lipid X, unveiling a unique insertion lid above the conserved architecture o...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/nmicrobiol.2016.154
更新日期:2016-08-15 00:00:00
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
更新日期:2017-06-12 00:00:00
abstract::Despite the sporadic detection of fluoroquinolone-resistant Shigella in Asia in the early 2000s and the subsequent global spread of ciprofloxacin-resistant (cipR) Shigella sonnei from 2010, fluoroquinolones remain the recommended therapy for shigellosis1-7. The potential for cipR S. sonnei to develop resistance to alt...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-019-0645-9
更新日期:2020-02-01 00:00:00
abstract:: ...
journal_title:Nature microbiology
pub_type: 评论,杂志文章
doi:10.1038/s41564-018-0277-5
更新日期:2018-11-01 00:00:00
abstract::The molecular processes that determine the outcome of influenza virus infection in humans are multifactorial and involve a complex interplay between host, viral and bacterial factors1. However, it is generally accepted that a strong innate immune dysregulation known as 'cytokine storm' contributes to the pathology of ...
journal_title:Nature microbiology
pub_type: 信件
doi:10.1038/s41564-018-0240-5
更新日期:2018-11-01 00:00:00
abstract::CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection1. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases2. While the essential requirements for immune activity are well under...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-020-0691-3
更新日期:2020-05-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature microbiology
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41564-020-0698-9
更新日期:2020-04-01 00:00:00
abstract:: ...
journal_title:Nature microbiology
pub_type: 社论
doi:10.1038/s41564-018-0320-6
更新日期:2018-12-01 00:00:00
abstract::Leishmania are ancient eukaryotes that have retained the exosome pathway through evolution. Leishmania RNA virus 1 (LRV1)-infected Leishmania species are associated with a particularly aggressive mucocutaneous disease triggered in response to the double-stranded RNA (dsRNA) virus. However, it is unclear how LRV1 is ex...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-018-0352-y
更新日期:2019-04-01 00:00:00
abstract::Evidence has accumulated to demonstrate that the intestinal microbiota enhances mammalian enteric virus infections1. For example, we and others previously reported that commensal bacteria stimulate acute and persistent murine norovirus infections2-4. However, in apparent contradiction of these results, the virulence o...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-019-0602-7
更新日期:2020-01-01 00:00:00
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
更新日期:2019-12-01 00:00:00
abstract::Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus with a high case mortality rate in humans. EEEV is a biodefence concern because of its potential for aerosol spread and the lack of existing countermeasures. Here, we identify a panel of 18 neutralizing murine monoclonal antibodies (mAbs) ag...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-018-0286-4
更新日期:2019-01-01 00:00:00
abstract::Bacterial toxin-antitoxin systems (TASs) are thought to respond to various stresses, often inducing growth-arrested (persistent) sub-populations of cells whose housekeeping functions are inhibited. Many such TASs induce this effect through the translation-dependent RNA cleavage (RNase) activity of their toxins, which ...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/nmicrobiol.2016.8
更新日期:2016-02-22 00:00:00
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
更新日期:2018-12-01 00:00:00
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
更新日期:2020-04-01 00:00:00
abstract::In structured environments, antibiotic-producing microorganisms can gain a selective advantage by inhibiting nearby competing species1. However, despite their genetic potential2,3, natural isolates often make only small amounts of antibiotics, and laboratory evolution can lead to loss rather than enhancement of antibi...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/nmicrobiol.2016.175
更新日期:2016-09-26 00:00:00
abstract::It is generally believed that exchange of secondary metabolite biosynthetic gene clusters (BGCs) among closely related bacteria is an important driver of BGC evolution and diversification. Applying this idea may help researchers efficiently connect many BGCs to their products and characterize the products' roles in va...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-019-0573-8
更新日期:2019-12-01 00:00:00
abstract::Most microorganisms live in environments where nutrients are limited and fluctuate over time. Cells respond to nutrient fluctuations by sensing and adapting their physiological state. Recent studies suggest phenotypic heterogeneity(1) in isogenic populations as an alternative strategy in fluctuating environments, wher...
journal_title:Nature microbiology
pub_type: 信件
doi:10.1038/nmicrobiol.2016.55
更新日期:2016-05-09 00:00:00
abstract::Retinoic acid-inducible gene I (RIG-I) receptor recognizes 5'-triphosphorylated RNA and triggers a signalling cascade that results in the induction of type-I interferon (IFN)-dependent responses. Its precise regulation represents a pivotal balance between antiviral defences and autoimmunity. To elucidate the cellular ...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/nmicrobiol.2017.22
更新日期:2017-03-01 00:00:00
abstract::As they proliferate, fungi expose antigens at their cell surface that are potent stimulators of the innate immune response, and yet the commensal fungus Candida albicans is able to colonize immuno competent individuals. We show that C. albicans may evade immune detection by presenting a moving immunological target. We...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/nmicrobiol.2016.238
更新日期:2016-12-12 00:00:00
abstract::Influenza A virus is a human pathogen with a genome composed of eight viral RNA segments that replicate in the nucleus. Two viral mRNAs are alternatively spliced. The unspliced M1 mRNA is translated into the matrix M1 protein, while the ion channel M2 protein is generated after alternative splicing. These proteins are...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/nmicrobiol.2016.69
更新日期:2016-05-27 00:00:00
abstract::Immune responses in insects are differentially triggered depending on the infection route used by the pathogen. In most studies involving Drosophila melanogaster and viruses, infection is done by injection, while oral infection, which is probably the most common route of viral entry in nature, remains unexplored. Here...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-018-0265-9
更新日期:2018-12-01 00:00:00
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
更新日期:2017-10-01 00:00:00
abstract::Little is known about the specificities and neutralization breadth of the H7-reactive antibody repertoire induced by natural H7N9 infection in humans. We have isolated and characterized 73 H7-reactive monoclonal antibodies from peripheral B cells from four donors infected in 2013 and 2014. Of these, 45 antibodies were...
journal_title:Nature microbiology
pub_type: 杂志文章
doi:10.1038/s41564-018-0303-7
更新日期:2019-02-01 00:00:00