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Herzig B.,Max Planck Institute for Chemistry | Yakulov T.A.,Max Planck Institute for Chemistry | Yakulov T.A.,University Hospital Freiburg | Klinge K.,Max Planck Institute for Chemistry | And 5 more authors.
Biology Open

Self-renewing stem cells are pools of undifferentiated cells, which are maintained in cellular niche environments by distinct tissuespecific signalling pathways. In Drosophila melanogaster, female germline stem cells (GSCs) are maintained in a somatic niche of the gonads by BMP signalling. Here we report a novel function of the Drosophila kinase Bällchen (BALL), showing that its cell autonomous role is to maintain the self-renewing capacity of female GSCs independent of BMP signalling. ball mutant GSCs are eliminated from the niche and subsequently differentiate into mature eggs, indicating that BALL is largely dispensable for differentiation. Similar to female GSCs, BALL is required to maintain self-renewal of male GSCs, suggesting a tissue independent requirement of BALL for self-renewal of germline stem cells. ©2014. Published by The Company of Biologists Ltd |. Source

Rieder R.,Max Planck Institute For Infektionsbiologie

Small non-coding RNAs (sRNAs) have received increasing attention as potent regulators of gene expression in virtually all organisms. We are particularly interested in the discovery and molecular characterization of such sRNAs in bacterial pathogens. Source

Schierack P.,Free University of Berlin | Kleta S.,Free University of Berlin | Kleta S.,Bundesinstitut For Risikobewertung | Tedin K.,Free University of Berlin | And 7 more authors.

Background: The probiotic Escherichia coli strain Nissle 1917 (EcN) has been shown to interfere in a human in vitro model with the invasion of several bacterial pathogens into epithelial cells, but the underlying molecular mechanisms are not known. Methodology/Principal Findings: In this study, we investigated the inhibitory effects of EcN on Salmonella Typhimurium invasion of porcine intestinal epithelial cells, focusing on EcN effects on the various stages of Salmonella infection including intracellular and extracellular Salmonella growth rates, virulence gene regulation, and adhesion. We show that EcN affects the initial Salmonella invasion steps by modulating Salmonella virulence gene regulation and Salmonella SiiE-mediated adhesion, but not extra- and intracellular Salmonella growth. However, the inhibitory activity of EcN against Salmonella invasion always correlated with EcN adhesion capacities. EcN mutants defective in the expression of F1C fimbriae and flagellae were less adherent and less inhibitory toward Salmonella invasion. Another E. coli strain expressing F1C fimbriae was also adherent to IPEC-J2 cells, and was similarly inhibitory against Salmonella invasion like EcN. Conclusions: We propose that EcN affects Salmonella adhesion through secretory components. This mechanism appears to be common to many E. coli strains, with strong adherence being a prerequisite for an effective reduction of SiiE-mediated Salmonella adhesion. © 2011 Schierack et al. Source

Heimesaat M.M.,Charite - Medical University of Berlin | Nogai A.,Charite - Medical University of Berlin | Bereswill S.,Charite - Medical University of Berlin | Plickert R.,Charite - Medical University of Berlin | And 8 more authors.

Background: The bacterial microflora aggravates graft-versus-host-disease (GvHD) after allogeneic stem cell transplantation, but the underlying mechanisms of manifestations of intestinal GvHD (iGvHD) in the gut remain poorly understood. Aim: To analyse the gut flora composition and the impact of bacterial sensing via Toll-like receptors (TLRs) in iGvHD. Methods: By mimicking clinical low-intensity conditioning regimens used in humans, a novel irradiation independent, treosulfan and cyclophosphamide-based murine allogeneic transplantation model was established. A global survey of the intestinal microflora by cultural and molecular methods was performed, the intestinal immunopathology in TLR-deficient recipient mice with iGvHD investigated and finally, the impact of anti-TLR9 treatment on iGvHD development assessed. Results: The inflammatory responses in iGvHD were accompanied by gut flora shifts towards enterobacteria, enterococci and Bacteroides/Prevotella spp. Analysis of iGvHD in MyD88 -/-, TRIF -/-, TLR2/4 -/-, and TLR9 -/- recipient mice showed that bacterial sensing via TLRs was essential for iGvHD development. Acute iGvHD was characterised by increasing numbers of apoptotic cells, proliferating cells, T cells and neutrophils within the colon. These responses were significantly reduced in MyD88 -/-, TLR2/4 -/-, TRIF -/- and TLR9 -/- mice, as compared with wild-type controls. However, TRIF-/- and TLR2/4 -/- mice were not protected from mortality, whereas TLR9 -/- mice displayed increased survival rates. The important role of TLR9-mediated immunopathology was independently confirmed by significantly reduced macroscopic disease symptoms and colonic apoptosis as well as by reduced T-cell and neutrophil numbers within the colon after treatment with a synthetic inhibitory oligonucleotide. Conclusions: These results emphasise the critical role of gut microbiota, innate immunity and TLR9 in iGvHD and highlight anti-TLR9 strategies as novel therapeutic options. Source

Moodley Y.,Max Planck Institute For Infektionsbiologie | Moodley Y.,University of Veterinary Medicine Vienna | Linz B.,Max Planck Institute For Infektionsbiologie | Linz B.,Pennsylvania State University | And 11 more authors.
PLoS Pathogens

When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88-116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43-56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36-52 kya, after the Out of Africa migrations around 60 kya. © 2012 Moodley et al. Source

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