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Cell Host & Microbe

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https://www.readbyqxmd.com/read/29398651/bacteroides-fragilis-toxin-coordinates-a-pro-carcinogenic-inflammatory-cascade-via-targeting-of-colonic-epithelial-cells
#1
Liam Chung, Erik Thiele Orberg, Abby L Geis, June L Chan, Kai Fu, Christina E DeStefano Shields, Christine M Dejea, Payam Fathi, Jie Chen, Benjamin B Finard, Ada J Tam, Florencia M McAllister, Hongni Fan, Xinqun Wu, Sudipto Ganguly, Andriana Lebid, Paul Metz, Sara W Van Meerbeke, David L Huso, Elizabeth C Wick, Drew M Pardoll, Fengyi Wan, Shaoguang Wu, Cynthia L Sears, Franck Housseau
Pro-carcinogenic bacteria have the potential to initiate and/or promote colon cancer, in part via immune mechanisms that are incompletely understood. Using ApcMin mice colonized with the human pathobiont enterotoxigenic Bacteroides fragilis (ETBF) as a model of microbe-induced colon tumorigenesis, we show that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic, multi-step inflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling in colonic epithelial cells (CECs). Although necessary, Stat3 activation in CECs is not sufficient to trigger ETBF colon tumorigenesis...
February 1, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29398650/tracking-vibrio-cholerae-cell-cell-interactions-during-infection-reveals-bacterial-population-dynamics-within-intestinal-microenvironments
#2
Yang Fu, Brian T Ho, John J Mekalanos
Vibrio cholerae is the causative agent of the diarrheal disease cholera. Although many V. cholerae virulence factors have been studied, the role of interbacterial interactions within the host gut and their influence on colonization are poorly understood. Here, we utilized the conjugative properties of a Vibrio-specific plasmid to serve as a quantifiable genetic marker for direct contact among V. cholerae cells in the infant rabbit model for cholera. In conjunction, we also quantified contact-dependent type 6 secretion system (T6SS)-mediated killing of co-infecting V...
February 1, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29398649/cytosolic-and-secreted-peptidoglycan-degrading-enzymes-in-drosophila-respectively-control-local-and-systemic-immune-responses-to-microbiota
#3
Bernard Charroux, Florence Capo, C Léopold Kurz, Sabine Peslier, Delphine Chaduli, Annelise Viallat-Lieutaud, Julien Royet
Gut-associated bacteria produce metabolites that both have a local influence on the intestinal tract and act at a distance on remote organs. In Drosophila, bacteria-derived peptidoglycan (PGN) displays such a dual role. PGN triggers local antimicrobial peptide production by enterocytes; it also activates systemic immune responses in fat-body cells and modulates fly behavior by acting on neurons. How these responses to a single microbiota-derived compound are simultaneously coordinated is not understood. We show here that the PGRP-LB locus generates both cytosolic and secreted PGN-cleaving enzymes...
January 30, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29396040/identification-of-a-botulinum-neurotoxin-like-toxin-in-a-commensal-strain-of-enterococcus-faecium
#4
Sicai Zhang, Francois Lebreton, Michael J Mansfield, Shin-Ichiro Miyashita, Jie Zhang, Julia A Schwartzman, Liang Tao, Geoffrey Masuyer, Markel Martínez-Carranza, Pål Stenmark, Michael S Gilmore, Andrew C Doxey, Min Dong
Botulinum neurotoxins (BoNTs), produced by various Clostridium strains, are a family of potent bacterial toxins and potential bioterrorism agents. Here we report that an Enterococcus faecium strain isolated from cow feces carries a BoNT-like toxin, designated BoNT/En. It cleaves both VAMP2 and SNAP-25, proteins that mediate synaptic vesicle exocytosis in neurons, at sites distinct from known BoNT cleavage sites on these two proteins. Comparative genomic analysis determines that the E. faecium strain carrying BoNT/En is a commensal type and that the BoNT/En gene is located within a typical BoNT gene cluster on a 206 kb putatively conjugative plasmid...
January 26, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29358084/intestinal-epithelial-cell-autophagy-is-required-to-protect-against-tnf-induced-apoptosis-during-chronic-colitis-in-mice
#5
Johanna Pott, Agnieszka Martyna Kabat, Kevin Joseph Maloy
Genome-wide association studies have linked polymorphisms in the autophagy gene ATG16L1 with susceptibility to inflammatory bowel disease (IBD). However, the cell-type-specific effects of autophagy on the regulation of chronic intestinal inflammation have not been investigated. Here, we assessed the effect of myeloid-specific or intestinal epithelial cell (IEC)-specific deletion of Atg16l1 on chronic colitis triggered by the intestinal opportunistic pathogen Helicobacter hepaticus in mice. Although Atg16l1 deficiency in myeloid cells had little effect on disease, mice selectively lacking Atg16l1 in IECs (Atg16l1VC) developed severely exacerbated pathology, accompanied by elevated pro-inflammatory cytokine secretion and increased IEC apoptosis...
January 17, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29358083/loss-of-paneth-cell-autophagy-causes-acute-susceptibility-to-toxoplasma-gondii-mediated-inflammation
#6
Elise Burger, Alessandra Araujo, Américo López-Yglesias, Michael W Rajala, Linda Geng, Beth Levine, Lora V Hooper, Ezra Burstein, Felix Yarovinsky
The protozoan parasite Toxoplasma gondii triggers severe small intestinal immunopathology characterized by IFN-γ- and intestinal microbiota-mediated inflammation, Paneth cell loss, and bacterial dysbiosis. Paneth cells are a prominent secretory epithelial cell type that resides at the base of intestinal crypts and releases antimicrobial peptides. We demonstrate that the microbiota triggers basal Paneth cell-specific autophagy via induction of IFN-γ, a known trigger of autophagy, to maintain intestinal homeostasis...
January 17, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29290576/leukotriene-b4-mediated-neutrophil-recruitment-causes-pulmonary-capillaritis-during-lethal-fungal-sepsis
#7
Esther K S Lee, Mark R Gillrie, Lu Li, Jason W Arnason, Jung Hwan Kim, Liane Babes, Yuefei Lou, Amir Sanati-Nezhad, Stephen K Kyei, Margaret M Kelly, Christopher H Mody, May Ho, Bryan G Yipp
Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflicted patients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C. albicans yeast in a lethal septic mouse and human pulmonary circulation model. Live C. albicans sequester to the endothelium and are immediately captured by complement-dependent PMN chemotaxis, which is required for host survival...
December 28, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29290575/bacteria-facilitate-enteric-virus-co-infection-of-mammalian-cells-and-promote-genetic-recombination
#8
Andrea K Erickson, Palmy R Jesudhasan, Melinda J Mayer, Arjan Narbad, Sebastian E Winter, Julie K Pfeiffer
RNA viruses exist in genetically diverse populations due to high levels of mutations, many of which reduce viral fitness. Interestingly, intestinal bacteria can promote infection of several mammalian enteric RNA viruses, but the mechanisms and consequences are unclear. We screened a panel of 41 bacterial strains as a platform to determine how different bacteria impact infection of poliovirus, a model enteric virus. Most bacterial strains, including those extracted from cecal contents of mice, bound poliovirus, with each bacterium binding multiple virions...
December 28, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29276171/bifidobacteria-or-fiber-protects-against-diet-induced-microbiota-mediated-colonic-mucus-deterioration
#9
Bjoern O Schroeder, George M H Birchenough, Marcus Ståhlman, Liisa Arike, Malin E V Johansson, Gunnar C Hansson, Fredrik Bäckhed
Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice...
December 16, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29276172/dysbiosis-associated-change-in-host-metabolism-generates-lactate-to-support-salmonella-growth
#10
Caroline C Gillis, Elizabeth R Hughes, Luisella Spiga, Maria G Winter, Wenhan Zhu, Tatiane Furtado de Carvalho, Rachael B Chanin, Cassie L Behrendt, Lora V Hooper, Renato L Santos, Sebastian E Winter
During Salmonella-induced gastroenteritis, mucosal inflammation creates a niche that favors the expansion of the pathogen population over the microbiota. Here, we show that Salmonella Typhimurium infection was accompanied by dysbiosis, decreased butyrate levels, and substantially elevated lactate levels in the gut lumen. Administration of a lactate dehydrogenase inhibitor blunted lactate production in germ-free mice, suggesting that lactate was predominantly of host origin. Depletion of butyrate-producing Clostridia, either through oral antibiotic treatment or as part of the pathogen-induced dysbiosis, triggered a switch in host cells from oxidative metabolism to lactate fermentation, increasing both lactate levels and Salmonella lactate utilization...
December 15, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29276170/fiber-mediated-nourishment-of-gut-microbiota-protects-against-diet-induced-obesity-by-restoring-il-22-mediated-colonic-health
#11
Jun Zou, Benoit Chassaing, Vishal Singh, Michael Pellizzon, Matthew Ricci, Michael D Fythe, Matam Vijay Kumar, Andrew T Gewirtz
Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43...
December 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447698/genetic-ablation-of-butyrate-utilization-attenuates-gastrointestinal-salmonella-disease
#12
Denise N Bronner, Franziska Faber, Erin E Olsan, Mariana X Byndloss, Nada A Sayed, Gege Xu, Woongjae Yoo, Dajeong Kim, Sangryeol Ryu, Carlito B Lebrilla, Andreas J Bäumler
Salmonella enterica serovar (S.) Typhi is an extraintestinal pathogen that evolved from Salmonella serovars causing gastrointestinal disease. Compared with non-typhoidal Salmonella serovars, the genomes of typhoidal serovars contain various loss-of-function mutations. However, the contribution of these genetic differences to this shift in pathogen ecology remains unknown. We show that the ydiQRSTD operon, which is deleted in S. Typhi, enables S. Typhimurium to utilize microbiota-derived butyrate during gastrointestinal disease...
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447697/herpes-simplex-virus-1-vp22-inhibits-aim2-dependent-inflammasome-activation-to-enable-efficient-viral-replication
#13
Yuhei Maruzuru, Takeshi Ichinohe, Ryota Sato, Kensuke Miyake, Tokuju Okano, Toshihiko Suzuki, Takumi Koshiba, Naoto Koyanagi, Shumpei Tsuda, Mizuki Watanabe, Jun Arii, Akihisa Kato, Yasushi Kawaguchi
The AIM2 inflammasome is activated by DNA, leading to caspase-1 activation and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-18, which are critical mediators in host innate immune responses against various pathogens. Some viruses employ strategies to counteract inflammasome-mediated induction of pro-inflammatory cytokines, but their in vivo relevance is less well understood. Here we show that the herpes simplex virus 1 (HSV-1) tegument protein VP22 inhibits AIM2-dependent inflammasome activation...
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447696/strain-tracking-reveals-the-determinants-of-bacterial-engraftment-in-the-human-gut-following-fecal-microbiota-transplantation
#14
Christopher S Smillie, Jenny Sauk, Dirk Gevers, Jonathan Friedman, Jaeyun Sung, Ilan Youngster, Elizabeth L Hohmann, Christopher Staley, Alexander Khoruts, Michael J Sadowsky, Jessica R Allegretti, Mark B Smith, Ramnik J Xavier, Eric J Alm
Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. We built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time...
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447695/cervicovaginal-microbiota-and-reproductive-health-the-virtue-of-simplicity
#15
REVIEW
Melis N Anahtar, David B Gootenberg, Caroline M Mitchell, Douglas S Kwon
Cervicovaginal microbiota play a critical role in women's health and reproductive outcomes. Despite being one of the simplest commensal bacterial communities in the human body, we are only beginning to appreciate its complex dynamic nature and important role in host immune modulation. In this review, we discuss the "optimal" cervicovaginal bacterial community composition, the impact of microbiota on gynecologic and obstetric outcomes, and the hurdles to developing a deeper mechanistic understanding of the function of the cervicovaginal microbiome...
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447694/an-additive-sugar-helps-the-c-diff-go-round
#16
Michael C Abt
Outbreaks of hypervirulent strains of Clostridium difficile began to be reported in healthcare facilities worldwide around 20 years ago. Concurrently, trehalose became a common additive used by the global food industry. A new study provides evidence that these two observations are a linked phenomenon (Collins et al., 2018).
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447693/infectious-scarring-setting-the-trigger-for-intestinal-inflammation
#17
Andrew M F Johnson, R William DePaolo
The initiating factors that trigger inflammatory bowel disease (IBD) are poorly understood. In a recent paper, Yang et al. (2017) demonstrate that IBD-like syndrome in mice can develop as a consequence of recurrent pathogen infection. Pathogenic triggering of inflammatory disease is a re-emerging concept that has significant therapeutic implications.
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447692/less-is-best-in-the-convergent-evolution-of-typhoidal-salmonella
#18
Andrés Vázquez-Torres
Related works in this issue of Cell Host & Microbe (Bronner et al., 2018) and in a recent issue of Cell Reports (Hiyoshi et al., 2018) demonstrate how loss-of-function mutations in butyrate utilization and lipopolysaccharide O-antigen processing contribute to evasion of innate host defenses and the convergent evolution of distinct typhoidal Salmonella lineages.
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447691/a-balancing-act-pgrps-preserve-and-protect
#19
Roman Dziarski, Dipika Gupta
How does the immune system maintain a balance between preserving a beneficial microbiome and protecting against pathogens while also inducing effective, yet not damaging, responses? In this issue of Cell Host & Microbe, Charroux et al. (2018) reveal that, in Drosophila, this task is performed by three isoforms of PGRP-LB, a peptidoglycan-hydrolyzing amidase.
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29447690/autophagy-suicide-prevention-hotline-for-the-gut-epithelium
#20
Mayara Grizotte-Lake, Shipra Vaishnava
Autophagy is genetically associated with inflammatory bowel disease (IBD); however, its role remains unclear in disease pathogenesis. Three recent studies reveal a novel cytoprotective role of autophagy during viral, bacterial, and protozoan-triggered IBD (Burger et al., 2018; Matsuzawa-Ishimoto et al., 2017; Pott et al., 2018).
February 14, 2018: Cell Host & Microbe
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