Sugar efflux transporters are essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development. Despite broad biological importance, the identity of sugar efflux transporters has remained elusive. Using optical glucose sensors, we identified a new class of sugar transporters, named SWEETs, and show that at least six out of seventeen Arabidopsis, two out of over twenty rice and two out of seven homologues in Caenorhabditis elegans, and the single copy human protein, mediate glucose transport. Arabidopsis SWEET8 is essential for pollen viability, and the rice homologues SWEET11 and SWEET14 are specifically exploited by bacterial pathogens for virulence by means of direct binding of a bacterial effector to the SWEET promoter. Bacterial symbionts and fungal and bacterial pathogens induce the expression of different SWEET genes, indicating that the sugar efflux function of SWEET transporters is probably targeted by pathogens and symbionts for nutritional gain. The metazoan homologues may be involved in sugar efflux from intestinal, liver, epididymis and mammary cells.The molecular nature of cellular sugar efflux in both plants and animals is unknown despite the fact that sugar efflux is an essential component for cellular exchange of carbon and energy in multicellular organisms [1][2][3][4] . Sugar efflux from the tapetum or transmitting tract of the style, for example, fuels pollen development and pollen tube growth 5 . Flowers secrete sugars for nectar production to attract pollinators, and plants secrete carbohydrates into the rhizosphere, potentially to feed beneficial microorganisms 6 . Sugar efflux carriers are

The bacterial pathogen Helicobacter pylori has co-evolved with humans and colonizes roughly one half of the human population, but only causes overt gastric disease in a subset of infected hosts. In this Review, we discuss the pathogenesis of this bacterium and the mechanisms it uses to promote persistent colonization of the gastric mucosa, with a focus on recent insights into the role of the virulence factors VacA, CagA and CagL. We also describe the immunobiology of H. pylori infection and highlight how this bacterium manipulates the innate and adaptive immune systems of the host to promote its own persistence.

The bacterial pathogen Helicobacter pylori chronically infects the human gastric mucosa and is the leading risk factor for the development of gastric cancer. The molecular mechanisms of H. pyloriassociated gastric carcinogenesis remain ill defined. In this study, we examined the possibility that H. pylori directly compromises the genomic integrity of its host cells. We provide evidence that the infection introduces DNA double-strand breaks (DSBs) in primary and transformed murine and human epithelial and mesenchymal cells. The induction of DSBs depends on the direct contact of live bacteria with mammalian cells. The infection-associated DNA damage is evident upon separation of nuclear DNA by pulse field gel electrophoresis and by high-magnification microscopy of metaphase chromosomes. Bacterial adhesion (e.g., via blood group antigenbinding adhesin) is required to induce DSBs; in contrast, the H. pylori virulence factors vacuolating cytotoxin A, γ-glutamyl transpeptidase, and the cytotoxin-associated gene (Cag) pathogenicity island are dispensable for DSB induction. The DNA discontinuities trigger a damage-signaling and repair response involving the sequential ataxia telangiectasia mutated (ATM)-dependent recruitment of repair factors-p53-binding protein (53BP1) and mediator of DNA damage checkpoint protein 1 (MDC1)-and histone H2A variant X (H2AX) phosphorylation. Although most breaks are repaired efficiently upon termination of the infection, we observe that prolonged active infection leads to saturation of cellular repair capabilities. In summary, we conclude that DNA damage followed by potentially imprecise repair is consistent with the carcinogenic properties of H. pylori and with its mutagenic properties in vitro and in vivo and may contribute to the genetic instability and frequent chromosomal aberrations that are a hallmark of gastric cancer.

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The human bacterial pathogen Helicobacter pylori exhibits genotoxic properties that promote gastric carcinogenesis. H. pylori introduces DNA double strand breaks (DSBs) in epithelial cells that trigger host cell DNA repair efforts. Here, we show that H. pylori-induced DSBs are repaired via error-prone, potentially mutagenic non-homologous end-joining. A genome-wide screen for factors contributing to DSB induction revealed a critical role for the H. pylori type IV secretion system (T4SS). Inhibition of transcription, as well as NF-κB/RelA-specific RNAi, abrogates DSB formation. DSB induction further requires β1-integrin signaling. DSBs are introduced by the nucleotide excision repair endonucleases XPF and XPG, which, together with RelA, are recruited to chromatin in a highly coordinated, T4SS-dependent manner. Interestingly, XPF/XPG-mediated DNA DSBs promote NF-κB target gene transactivation and host cell survival. In summary, H. pylori induces XPF/XPG-mediated DNA damage through activation of the T4SS/β1-integrin signaling axis, which promotes NF-κB target gene expression and host cell survival.

BACKGROUND The Gram-negative bacterium Helicobacter pylori is a constituent of the human gastric microbiota. Chronic infection with H. pylori causes gastritis and predisposes to gastric carcinoma but has also been inversely linked to various allergic and chronic inflammatory conditions. In particular, large meta-analyses have documented an inverse association between H. pylori infection and the risk of developing ulcerative colitis and Crohn's disease. METHODS We investigated possible protective effects of experimental H. pylori infection and of regular treatment with H. pylori extract in 2 mouse models of colitis and in mouse models of type I diabetes and multiple sclerosis. The mechanism of protection was examined in mouse strains lacking specific innate immune recognition pathways and cytokines. RESULTS We show here that experimental infection with H. pylori and administration of regular doses of H. pylori extract both alleviate the clinical and histopathological features of dextran sodium sulfateinduced chronic colitis and of T-cell transfer-induced colitis. High resolution endoscopy of the protected animals revealed the accumulation of large amounts of colonic mucus upon H. pylori exposure, which could be attributed to transcriptional activation of the mucin 2 gene. The protection against dextran sodium sulfate-induced colitis was dependent on the NLRP3 inflammasome and interleukin-18 signaling. Other autoimmune diseases, i.e., experimental autoimmune encephalomyelitis and type I diabetes, were not controlled by H. pylori. CONCLUSIONS In summary, we propose here that the immunomodulatory activity of an ancient constituent of the gut microbiota, H. pylori, may be exploited for the prevention and/or treatment of inflammatory bowel diseases.

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