@article{SieglPrustyKarunakaranetal.2014, author = {Siegl, Christine and Prusty, Bhupesh K. and Karunakaran, Karthika and Wischhusen, J{\"o}rg and Rudel, Thomas}, title = {Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection}, series = {Cell Reports}, volume = {9}, journal = {Cell Reports}, number = {3}, issn = {2211-1247}, doi = {10.1016/j.celrep.2014.10.004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118200}, pages = {918-929}, year = {2014}, abstract = {Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.}, language = {en} } @article{BaurRautenbergFaulstichetal.2014, author = {Baur, Stefanie and Rautenberg, Maren and Faulstich, Manuela and Grau, Timo and Severin, Yannik and Unger, Clemens and Hoffmann, Wolfgang H. and Rudel, Thomas and Autenrieth, Ingo B. and Weidenmaier, Christopher}, title = {A Nasal Epithelial Receptor for Staphylococcus aureus WTA Governs Adhesion to Epithelial Cells and Modulates Nasal Colonization}, series = {PLOS PATHOGENS}, volume = {10}, journal = {PLOS PATHOGENS}, number = {5}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1004089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116280}, pages = {e1004089}, year = {2014}, abstract = {Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization.}, language = {en} } @article{VolceanovHerbstBiniosseketal.2014, author = {Volceanov, Larisa and Herbst, Katharina and Biniossek, Martin and Schilling, Oliver and Haller, Dirk and N{\"o}lke, Thilo and Subbarayal, Prema and Rudel, Thomas and Zieger, Barbara and H{\"a}cker, Georg}, title = {Septins Arrange F-Actin-Containing Fibers on the Chlamydia trachomatis Inclusion and Are Required for Normal Release of the Inclusion by Extrusion}, series = {MBIO}, volume = {5}, journal = {MBIO}, number = {5}, issn = {2150-7511}, doi = {10.1128/mBio.01802-14}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115421}, pages = {e01802-14}, year = {2014}, abstract = {Chlamydia trachomatis is an obligate intracellular human pathogen that grows inside a membranous, cytosolic vacuole termed an inclusion. Septins are a group of 13 GTP-binding proteins that assemble into oligomeric complexes and that can form higher-order filaments. We report here that the septins SEPT2, -9, -11, and probably -7 form fibrillar structures around the chlamydial inclusion. Colocalization studies suggest that these septins combine with F actin into fibers that encase the inclusion. Targeting the expression of individual septins by RNA interference (RNAi) prevented the formation of septin fibers as well as the recruitment of actin to the inclusion. At the end of the developmental cycle of C. trachomatis, newly formed, infectious elementary bodies are released, and this release occurs at least in part through the organized extrusion of intact inclusions. RNAi against SEPT9 or against the combination of SEPT2/7/9 substantially reduced the number of extrusions from a culture of infected HeLa cells. The data suggest that a higher-order structure of four septins is involved in the recruitment or stabilization of the actin coat around the chlamydial inclusion and that this actin recruitment by septins is instrumental for the coordinated egress of C. trachomatis from human cells. The organization of F actin around parasite-containing vacuoles may be a broader response mechanism of mammalian cells to the infection by intracellular, vacuole-dwelling pathogens. IMPORTANCE Chlamydia trachomatis is a frequent bacterial pathogen throughout the world, causing mostly eye and genital infections. C. trachomatis can develop only inside host cells; it multiplies inside a membranous vacuole in the cytosol, termed an inclusion. The inclusion is covered by cytoskeletal "coats" or "cages," whose organization and function are poorly understood. We here report that a relatively little-characterized group of proteins, septins, is required to organize actin fibers on the inclusion and probably through actin the release of the inclusion. Septins are a group of GTP-binding proteins that can organize into heteromeric complexes and then into large filaments. Septins have previously been found to be involved in the interaction of the cell with bacteria in the cytosol. Our observation that they also organize a reaction to bacteria living in vacuoles suggests that they have a function in the recognition of foreign compartments by a parasitized human cell.}, language = {en} } @article{RemmeleXianAlbrechtetal.2014, author = {Remmele, Christian W. and Xian, Yibo and Albrecht, Marco and Faulstich, Michaela and Fraunholz, Martin and Heinrichs, Elisabeth and Dittrich, Marcus T. and M{\"u}ller, Tobias and Reinhardt, Richard and Rudel, Thomas}, title = {Transcriptional landscape and essential genes of Neisseria gonorrhoeae}, doi = {10.1093/nar/gku762}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113676}, year = {2014}, abstract = {The WHO has recently classified Neisseria gonorrhoeae as a super-bacterium due to the rapid spread of antibiotic resistant derivatives and an overall dramatic increase in infection incidences. Genome sequencing has identified potential genes, however, little is known about the transcriptional organization and the presence of non-coding RNAs in gonococci. We performed RNA sequencing to define the transcriptome and the transcriptional start sites of all gonococcal genes and operons. Numerous new transcripts including 253 potentially non-coding RNAs transcribed from intergenic regions or antisense to coding genes were identified. Strikingly, strong antisense transcription was detected for the phase-variable opa genes coding for a family of adhesins and invasins in pathogenic Neisseria, that may have regulatory functions. Based on the defined transcriptional start sites, promoter motifs were identified. We further generated and sequenced a high density Tn5 transposon library to predict a core of 827 gonococcal essential genes, 133 of which have no known function. Our combined RNA-Seq and Tn-Seq approach establishes a detailed map of gonococcal genes and defines the first core set of essential gonococcal genes.}, language = {en} } @article{RudelPrustySiegletal.2014, author = {Rudel, Thomas and Prusty, Bhupesh K. and Siegl, Christine and Gulve, Nitish and Mori, Yasuko}, title = {GP96 Interacts with HHV-6 during Viral Entry and Directs It for Cellular Degradation}, doi = {10. 1371/journal.pone.0113962}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111068}, year = {2014}, abstract = {CD46 and CD134 mediate attachment of Human Herpesvirus 6A (HHV-6A) and HHV-6B to host cell, respectively. But many cell types interfere with viral infection through rapid degradation of viral DNA. Hence, not all cells expressing these receptors are permissive to HHV-6 DNA replication and production of infective virions suggesting the involvement of additional factors that influence HHV-6 propagation. Here, we used a proteomics approach to identify other host cell proteins necessary for HHV-6 binding and entry. We found host cell chaperone protein GP96 to interact with HHV-6A and HHV-6B and to interfere with virus propagation within the host cell. In human peripheral blood mononuclear cells (PBMCs), GP96 is transported to the cell surface upon infection with HHV-6 and interacts with HHV-6A and -6B through its C-terminal end. Suppression of GP96 expression decreased initial viral binding but increased viral DNA replication. Transient expression of human GP96 allowed HHV-6 entry into CHO-K1 cells even in the absence of CD46. Thus, our results suggest an important role for GP96 during HHV-6 infection, which possibly supports the cellular degradation of the virus.}, language = {en} }