We have identified desmoglein 2 (DSG2) as the primary high-affinity receptor used by adenovirus (Ad) serotypes Ad3, Ad7, and Ad14. These serotypes represent important human pathogens causing respiratory tract infections. In epithelial cells, adenovirus binding to DSG2 triggers events reminiscent of epithelial-to-mesenchymal transition, leading to transient opening of intercellular junctions. This improves access to receptors, e.g. CD46 and Her2/neu, that are trapped in intercellular junctions. In addition to complete virions, dodecahedral particles (PtDd) formed by viral penton and fiber in excess during viral replication, can trigger DSG2-mediated opening of intercellular junctions as shown by studies with recombinant Ad3 PtDd. Our findings shed light on adenovirus biology and pathogenesis and have implications for cancer therapy.
Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14.
Specimen part
View SamplesStaphylococcus aureus thymidine-dependent small-colony variants (TD-SCVs) are frequently isolated from patients with chronic S. aureus infections after long-term treatment with trimethoprim-sulfamethoxazole (TMP-SMX). In TD-SCVs, mutations of thymidylate synthase (thyA, TS), essential for DNA synthesis, occur. However, it has never been shown, that TMP-SMX is responsible for the induction and selection of TD-SCVs. Short-term exposure of TMP-SMX induced the TD-SCV phenotype morphologically as shown in transmission electron-microscopy and on the transcriptional level by qRT-PCR in wild-type S. aureus, while selection of TD-SCVs with thyA mutations occurred only rarely after long-term exposure. In reversion experiments with clinical TD-SCVs, all revertants revealed compensating mutations at the initially identified mutation site. Whole DNA microarray analysis of a thyA deletion mutant (thyA), which exhibited the typical TD-SCV phenotype, identified tremendous alterations compared to the wild-type. Important virulence regulators such as agr, arlRS, sarA and major virulence determinants including hla, hlb, sspA, sspB and geh were down-regulated, while genes associated with the colonization capacity like fnbA, fnbB, spa, clfB, sdrC and sdrD were up-regulated. The expression of genes involved in pyrimidine and purine metabolism as well as in nucleotide interconversion changed significantly. The thyA-mutant was attenuated in virulence in both, a Caenorhabditis elegans killing model and an acute murine pneumonia model. Furthermore, competition experiments in vitro and in vivo (using a chronic pneumonia mouse model) revealed a survival and growth advantage of the thyA-mutant under low thymidine conditions and TMP-SMX exposure. In conclusion, our results clearly show for the first time that TMP-SMX induces the TD-SCV phenotype after short-term exposure in S. aureus and that long-term exposure selects thyA mutations providing an advantage for TD-SCVs under specified conditions. Thus, our results help to understand the dynamic processes of induction and selection of S. aureus TD-SCVs during TMP-SMX exposure.
Inactivation of thyA in Staphylococcus aureus attenuates virulence and has a strong impact on metabolism and virulence gene expression.
Time
View SamplesFundamental research and drug development for personalized medicine necessitates cell cultures from defined genetic backgrounds. However, providing sufficient numbers of authentic cells from individuals poses a challenge. Here, we present a new strategy for rapid cell expansion that overcomes current limitations. Using a small gene library, we expanded primary cells from different tissues, donors and species. Cell type specific regimens that allow the reproducible creation of cell lines were identified. In depth characterization of a series of endothelial and hepatocytic cell lines confirmed phenotypic stability and functionality. Applying this technology enables rapid, efficient and reliable production of unlimited numbers of personalized cells. As such, these cell systems support mechanistic studies, epidemiological research and tailored drug development.
Expansion of functional personalized cells with specific transgene combinations.
Specimen part
View SamplesHeterozygous and homozygous Pax2 E11.5 embryos were collected and the intermediate mesoderm was dissected and dispersed into single cells.
Evidence for intermediate mesoderm and kidney progenitor cell specification by Pax2 and PTIP dependent mechanisms.
Specimen part
View SamplesEpstein-Barr virus (EBV) is a ubiquitous gammaherpes virus that establishes a life-long latency in over 90% of the world's population. Epstein Barr Nuclear Antigen 1, EBNA1, is the only viral protein consistently detected in all viral latency programs, as well as in all forms of EBV-associated malignancies. EBNA1 plays critical roles in the viral life cycle by fostering the replication and maintenance of the extrachromosomal viral genome as well as enhancing transcription from multiple viral promoters.
Identifying sites bound by Epstein-Barr virus nuclear antigen 1 (EBNA1) in the human genome: defining a position-weighted matrix to predict sites bound by EBNA1 in viral genomes.
No sample metadata fields
View SamplesLiver RNA was collected from three genotypes: WT controls, KCP knockout (KCP-KO) mutants, and KCP-Transgenic (KCP-Tg) overexpressing mice.
The kielin/chordin-like protein KCP attenuates nonalcoholic fatty liver disease in mice.
Specimen part
View SamplesGlomerular RNA comparison between wild-type and podocyte specific deletion of the PTIP gene in 1 month old kidneys. The PTIP gene was deleted using a floxed allele and a Podocin-Cre driver strain.
Altering a histone H3K4 methylation pathway in glomerular podocytes promotes a chronic disease phenotype.
Specimen part
View SamplesGene expression profiles of peripheral blood samples from C57BL/6 mice exposed with ionizing radiation.
Biological pathway selection through Bayesian integrative modeling.
Sex, Specimen part, Treatment, Time
View SamplesLesions of chronic idiopathic urticaria (CIU) showed significant up-regulation of 506 genes and reduced expression of 51 genes.
Gene expression profiles in chronic idiopathic (spontaneous) urticaria.
Specimen part, Subject
View SamplesBacteria are extremely versatile organisms which rapidly adapt to changing environments. When Escherichia coli cells switch from planktonic growth to biofilm, flagellum formation is turned off, and the production of fimbriae and extracellular polysaccharides is switched on. Here we show that BolA protein is a new bacterial transcription factor which modulates the switch from planktonic to sessile lifestyle. BolA negatively modulates flagella biosynthesis and thus swimming capacity. Furthermore, BolA overexpression favors biofilm formation and involvesinvolving fimbriae-like adhesins and curli production. Our results unraveled for the first time that BolA is a protein with high affinity to DNA, involved in the regulation of several genes of E. coli at a genome-wide scale level. Moreover, this observation further demonstrated that the most significant targets of this protein involved a complex network of genes encoding proteins extremely necessary in biofilm development processes. Herein we propose that BolA is a motile/adhesive transcriptional switch, specifically involved in the transition between the planktonic and the attachment stage of biofilm formation process.
BolA is a transcriptional switch that turns off motility and turns on biofilm development.
No sample metadata fields
View Samples