| 1. |
- Bahram, Mohammad
(författare)
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Dispersal strategies shape persistence and evolution of human gut bacteria
- 2021
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Ingår i: Cell Host & Microbe. - : Elsevier BV. - 1931-3128. ; 29, s. 1167-1176
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Tidskriftsartikel (refereegranskat)abstract
- Human gut bacterial strains can co-exist with their hosts for decades, but little is known about how these microbes persist and disperse, and evolve thereby. Here, we examined these processes in 5,278 adult and infant fecal metagenomes, longitudinally sampled in individuals and families. Our analyses revealed that a subset of gut species is extremely persistent in individuals, families, and geographic regions, represented often by locally successful strains of the phylum Bacteroidota. These ''tenacious'' bacteria show high levels of genetic adaptation to the human host but a high probability of loss upon antibiotic interventions. By contrast, heredipersistent bacteria, notably Firmicutes, often rely on dispersal strategies with weak phylogeographic patterns but strong family transmissions, likely related to sporulation. These analyses describe how different dispersal strategies can lead to the long-term persistence of human gut microbes with implications for gut flora modulations.
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| 2. |
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| 3. |
- Besnard, E, et al.
(författare)
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The mTOR Complex Controls HIV Latency
- 2016
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Ingår i: Cell host & microbe. - : Elsevier BV. - 1934-6069 .- 1931-3128. ; 20:6, s. 785-797
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Billker, Oliver, et al.
(författare)
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Calcium Builds Strong Host-Parasite Interactions
- 2015
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Ingår i: Cell Host and Microbe. - : Elsevier. - 1931-3128 .- 1934-6069. ; 18:1, s. 9-10
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Forskningsöversikt (refereegranskat)abstract
- Apicomplexan parasite invasion of host cells is a multistep process, requiring coordinated events. In this issue of Cell Host & Microbe, Paul et al. (2015) and Philip and Waters (2015) leverage experimental genetics to show that the calcium-regulated protein phosphatase, calcinuerin, regulates invasion in multiple parasite species.
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| 5. |
- Billker, Oliver, et al.
(författare)
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Calcium-dependent signaling and kinases in apicomplexan parasites
- 2009
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 5:6, s. 612-622
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Tidskriftsartikel (refereegranskat)abstract
- Calcium controls many critical events in the complex life cycles of apicomplexan parasites including protein secretion, motility, and development. Calcium levels are normally tightly regulated and rapid release of calcium into the cytosol activates a family of calcium-dependent protein kinases (CDPKs), which are normally characteristic of plants. CDPKs present in apicomplexans have acquired a number of unique domain structures likely reflecting their diverse functions. Calcium regulation in parasites is closely linked to signaling by cyclic nucleotides and their associated kinases. This Review summarizes the pivotal roles that calcium- and cyclic nucleotide-dependent kinases play in unique aspects of parasite biology.
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| 6. |
- Billker, Oliver
(författare)
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CRISPRing the elephant in the room
- 2018
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Ingår i: Cell Host and Microbe. - : Elsevier. - 1931-3128 .- 1934-6069. ; 24:6, s. 754-755
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The importance of guanylyl-cyclases (GCs) in apicomplexa has remained elusive due to the large size of the genes. Two recent studies, including Brown and Sibley, 2018 in this issue of Cell Host & Microbe, make elegant use of genome editing with CRISPR-Cas9 to characterize roles of GCs in Toxoplasma and Plasmodium.
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| 7. |
- Blomgran, Robert, et al.
(författare)
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Mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to delayed activation of naive CD4 T cells
- 2012
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Ingår i: Cell Host and Microbe. - : Elsevier. - 1931-3128 .- 1934-6069. ; 11:1, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium tuberculosis promotes its replication by inhibiting the apoptosis of infected macrophages. A proapoptotic M. tuberculosis mutant lacking nuoG, a subunit of the type I NADH dehydrogenase complex, exhibits attenuated growth in vivo, indicating that this virulence mechanism is essential. We show that M. tuberculosis also suppresses neutrophil apoptosis. Compared to wild-type, the nuoG mutant spread to a larger number of lung phagocytic cells. Consistent with the shorter lifespan of infected neutrophils, infection with the nuoG mutant resulted in fewer bacteria per infected neutrophil, accelerated bacterial acquisition by dendritic cells, earlier trafficking of these dendritic cells to lymph nodes, and faster CD4 T cell priming. Neutrophil depletion abrogated accelerated CD4 T cell priming by the nuoG mutant, suggesting that inhibiting neutrophil apoptosis delays adaptive immunity in tuberculosis. Thus, pathogen modulation of apoptosis is beneficial at multiple levels, and enhancing phagocyte apoptosis promotes CD4 as well as CD8 T cell responses.
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| 8. |
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| 9. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Defining a Healthy Human Gut Microbiome: Current Concepts, Future Directions, and Clinical Applications
- 2012
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Ingår i: Cell Host & Microbe. - : Elsevier BV. - 1931-3128. ; 12:5, s. 611-622
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Tidskriftsartikel (refereegranskat)abstract
- Indigenous microbiota are an essential component in the modern concept of human health, but the composition and functional characteristics of a healthy microbiome remain to be precisely defined. Patterns of microbial colonization associated with disease states have been documented, but the health-associated microbial patterns and their functional characteristics are less clear. A healthy microbiome, considered in the context of body habitat or body site, could be described in terms of ecologic stability (i.e., ability to resist community structure change under stress or to rapidly return to baseline following a stress-related change), by an idealized (presumably health-associated) composition or by a desirable functional profile (including metabolic and trophic provisions to the host). Elucidation of the properties of healthy microbiota would provide a target for dietary interventions and/or microbial modifications aimed at sustaining health in generally healthy populations and improving the health of individuals exhibiting disrupted microbiota and associated diseases.
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| 10. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life
- 2015
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Ingår i: Cell Host & Microbe. - Cambridge : Elsevier BV. - 1931-3128 .- 1934-6069. ; 17:5, s. 690-703
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
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| 11. |
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| 12. |
- Carvalho, F. A., et al.
(författare)
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Transient Inability to Manage Proteobacteria Promotes Chronic Gut Inflammation in TLR5-Deficient Mice
- 2012
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Ingår i: Cell Host & Microbe. - : Elsevier BV. - 1931-3128. ; 12:2, s. 139-152
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Tidskriftsartikel (refereegranskat)abstract
- Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E. coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E. coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis.
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| 13. |
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| 14. |
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| 15. |
- Coppi, Alida, et al.
(författare)
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Heparan sulfate proteoglycans provide a signal to Plasmodium sporozoites to stop migrating and productively invade host cells
- 2007
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Ingår i: Cell Host and Microbe. - : Cell Press. - 1931-3128 .- 1934-6069. ; 2:5, s. 316-327
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Tidskriftsartikel (refereegranskat)abstract
- Malaria infection is initiated when Anopheles mosquitoes inject Plasmodium sporozoites into the skin. Sporozoites subsequently reach the liver, invading and developing within hepatocytes. Sporozoites contact and traverse many cell types as they migrate from skin to liver; however, the mechanism by which they switch from a migratory mode to an invasive mode is unclear. Here, we show that sporozoites of the rodent malaria parasite Plasmodium berghei use the sulfation level of host heparan sulfate proteoglycans (HSPGs) to navigate within the mammalian host. Sporozoites migrate through cells expressing low-sulfated HSPGs, such as those in skin and endothelium, while highly sulfated HSPGs of hepatocytes activate sporozoites for invasion. A calcium-dependent protein kinase is critical for the switch to an invasive phenotype, a process accompanied by proteolytic cleavage of the sporozoite's major surface protein. These findings explain how sporozoites retain their infectivity for an organ that is far from their site of entry.
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| 16. |
- Dolowschiak, Tamas, et al.
(författare)
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IFN-γ Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection.
- 2016
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- Salmonella Typhimurium (S.Tm) causes acute enteropathy resolving after 4-7 days. Strikingly, antibiotic therapy does not accelerate disease resolution. We screened for factors blocking remission using a S.Tm enterocolitis model. The antibiotic ciprofloxacin clears pathogen stool loads within 3-24 hr, while gut pathology resolves more slowly (ψ50: ∼48 hr, remission: 6-9 days). This delayed resolution is mediated by an interferon-γ (IFN-γ)-dependent response that is triggered during acute infection and continues throughout therapy. Specifically, IFN-γ production by mucosal T and NK cells retards disease resolution by maintaining signaling through the transcriptional regulator STAT1 and boosting expression of inflammatory mediators like IL-1β, TNF, and iNOS. Additionally, sustained IFN-γ fosters phagocyte accumulation and hampers antimicrobial defense mediated by IL-22 and the lectin REGIIIβ. These findings reveal a role for IFN-γ in delaying resolution of intestinal inflammation and may inform therapies for acute Salmonella enteropathy, chronic inflammatory bowel diseases, or disease resolution during antibiotic treatment.
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| 17. |
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| 18. |
- Earle, K. A., et al.
(författare)
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Quantitative Imaging of Gut Microbiota Spatial Organization
- 2015
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128. ; 18:4, s. 478-488
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Tidskriftsartikel (refereegranskat)abstract
- Summary Genomic technologies have significantly advanced our understanding of the composition and diversity of host-associated microbial populations. However, their spatial organization and functional interactions relative to the host have been more challenging to study. Here we present a pipeline for the assessment of intestinal microbiota localization within immunofluorescence images of fixed gut cross-sections that includes a flexible software package, BacSpace, for high-throughput quantification of microbial organization. Applying this pipeline to gnotobiotic and human microbiota-colonized mice, we demonstrate that elimination of microbiota-accessible carbohydrates (MACs) from the diet results in thinner mucus in the distal colon, increased proximity of microbes to the epithelium, and heightened expression of the inflammatory marker REG3β. Measurements of microbe-microbe proximity reveal that a MAC-deficient diet alters monophyletic spatial clustering. Furthermore, we quantify the invasion of Helicobacter pylori into the glands of the mouse stomach relative to host mitotic progenitor cells, illustrating the generalizability of this approach. © 2015 Elsevier Inc.
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| 19. |
- Enav, H., et al.
(författare)
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The developing infant gut microbiome: A strain-level view
- 2022
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128. ; 30:5, s. 627-638
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Forskningsöversikt (refereegranskat)abstract
- At birth, neonates provide a vast habitat awaiting microbial colonization. Microbiome assembly is a complex process involving microbial seeding and succession driven by ecological forces and subject to environmental conditions. These successional events not only significantly affect the ecology and function of the microbiome, but also impact host health. While the establishment of the infant microbiome has been a point of interest for decades, an integrated view focusing on strain level colonization has been lacking until recently. Technological and computational advancements enabling strain-level analyses of the infant microbiome have demonstrated the immense complexity of this system and allowed for an improved understanding of how strains of the same species spread, colonize, evolve, and affect the host. Here, we review the current knowledge of the establishment and maturation of the infant gut microbiome with particular emphasis on newer discoveries achieved through strain-centric analyses.
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| 20. |
- Gomes, Ana Rita, et al.
(författare)
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A genome-scale vector resource enables high-throughput reverse genetic screening in a malaria parasite
- 2015
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Ingår i: Cell Host and Microbe. - : Cell Press. - 1931-3128 .- 1934-6069. ; 17:3, s. 404-413
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Tidskriftsartikel (refereegranskat)abstract
- The genome-wide identification of gene functions in malaria parasites is hampered by a lack of reverse genetic screening methods. We present a large-scale resource of barcoded vectors with long homology arms for effective modification of the Plasmodium berghei genome. Cotransfecting dozens of vectors into the haploid blood stages creates complex pools of barcoded mutants, whose competitive fitness can be measured during infection of a single mouse using barcode sequencing (barseq). To validate the utility of this resource, we rescreen the P. berghei kinome, using published kinome screens for comparison. We find that several protein kinases function redundantly in asexual blood stages and confirm the targetability of kinases cdpk1, gsk3, tkl3, and PBANKA_082960 by genotyping cloned mutants. Thus, parallel phenotyping of barcoded mutants unlocks the power of reverse genetic screening for a malaria parasite and will enable the systematic identification of genes essential for in vivo parasite growth and transmission.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Herp, Simone, et al.
(författare)
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Mucispirillum schaedleri Antagonizes Salmonella Virulence to Protect Mice against Colitis
- 2019
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 25:5, s. 681-694.e8
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Tidskriftsartikel (refereegranskat)abstract
- The microbiota and the gastrointestinal mucus layer play a pivotal role in protection against non-typhoidal Salmonella enterica serovar Typhimurium (S. Tm) colitis. Here, we analyzed the course of Salmonella colitis in mice lacking a functional mucus layer in the gut. Unexpectedly, in contrast to mucus-proficient littermates, genetically deficient mice were protected against Salmonellainduced gut inflammation in the streptomycin colitis model. This correlated with microbiota alterations and enrichment of the bacterial phylum Deferribacteres. Using gnotobiotic mice associated with defined bacterial consortia, we causally linked Mucispirillum schaedleri, currently the sole known representative of Deferribacteres present in the mammalian microbiota, to host protection against S. Tm colitis. Inhibition by M. schaedleri involves interference with S. Tm invasion gene expression, partly by competing for anaerobic electron acceptors. In conclusion, this study establishes M. schaedleri, a core member of the murine gut microbiota, as a key antagonist of S. Tm virulence in the gut.
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| 25. |
- Hickey, C. A., et al.
(författare)
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Colitogenic Bacteroides thetaiotaomicron Antigens Access Host Immune Cells in a Sulfatase-Dependent Manner via Outer Membrane Vesicles
- 2015
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Ingår i: Cell Host & Microbe. - : Elsevier BV. - 1931-3128. ; 17:5, s. 672-680
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Tidskriftsartikel (refereegranskat)abstract
- Microbes interact with the host immune system via several potential mechanisms. One essential step for each mechanismis themethod by which intestinal microbes or their antigens access specific host immune cells. Using genetically susceptible mice (dnKO) that develop spontaneous, fulminant colitis, triggered by Bacteroides thetaiotaomicron (B. theta), we investigated the mechanism of intestinal microbial access under conditions that stimulate colonic inflammation. B. theta antigens localized to host immune cells through outer membrane vesicles (OMVs) that harbor bacterial sulfatase activity. We deleted the anaerobic sulfatase maturating enzyme (anSME) from B. theta, which is required for post-translational activation of all B. theta sulfatase enzymes. This bacterial mutant strain did not stimulate colitis in dnKO mice. Lastly, access of B. theta OMVs to host immune cells was sulfatase dependent. These data demonstrate that bacterial OMVs and associated enzymes promote inflammatoryimmune stimulation in genetically susceptible hosts.
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