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Heidelberg, Germany

Reipschlager S.,Albert Ludwigs University of Freiburg | Kubatzky K.,Medical Microbiology and Hygiene | Taromi S.,Albert Ludwigs University of Freiburg | Burger M.,Albert Ludwigs University of Freiburg | And 3 more authors.
Journal of Biological Chemistry | Year: 2012

RhoA is reportedly involved in signal transducers and activators of transcription (STAT)-dependent transcription. However, the pathway connecting the GTPase and STAT signaling has not been characterized. Here, we made use of bacterial toxins, which directly activate Rho GTPases to analyze this pathway. Cytotoxic necrotizing factors (CNFs) are produced by pathogenic Escherichia coli strains and by Yersinia pseudotuberculosis. They activate small GTPases of the Rho family by deamidation of a glutamine, which is crucial for GTP hydrolysis. We show that RhoA activation leads to phosphorylation and activation of STAT3 and identify signal proteins involved in this pathway. RhoA-dependent STAT3 stimulation requires ROCK and Jun kinase activation as well as AP1-induced protein synthesis. The secretion of one or more factors activates the JAK-STAT pathway in an auto/paracrine manner. We identify CCL1/I-309 as an essential cytokine, which is produced and secreted upon RhoA activation and which is able to activate STAT3-dependent signaling pathways. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

Lamerz A.-C.,Hannover Medical School | Damerow S.,Medical Microbiology and Hygiene | Kleczka B.,Roche Holding AG | Wiese M.,HZM Pharmaservice | And 10 more authors.
Glycobiology | Year: 2010

The nucleotide sugar UDP-galactose (UDP-Gal) is essential for the biosynthesis of several abundant glycoconjugates forming the surface glycocalyx of the protozoan parasite Leishmania major. Current data suggest that UDP-Gal could arise de novo by epimerization of UDP-glucose (UDP-Glc) or by a salvage pathway involving phosphorylation of Gal and the action of UDP-glucose: α-D-galactose-1-phosphate uridylyltransferase as described by Leloir. Since both pathways require UDP-Glc, inactivation of the UDP-glucose pyrophosphorylase (UGP) catalyzing activation of glucose-1 phosphate to UDP-Glc was expected to deprive parasites of UDP-Gal required for Leishmania glycocalyx formation. Targeted deletion of the gene encoding UGP, however, only partially affected the synthesis ofthe Gal-rich phosphoglycans. Moreover, no alteration in the abundant Gal-containing glycoinositolphospholipids was found in the deletion mutant. Consistent with these findings, the virulence of the UGP-deficient mutant was only modestly affected. These data suggest that Leishmania elaborates a UDP-Glc independent salvage pathway for UDP-Gal biosynthesis. © The Author 2010. Published by Oxford University Press. All rights reserved.

Jakob E.,The Interdisciplinary Center | Max R.,The Interdisciplinary Center | Zimmermann S.,Medical Microbiology and Hygiene | Dalpke A.H.,Medical Microbiology and Hygiene | And 3 more authors.
Ocular Immunology and Inflammation | Year: 2014

Purpose: Overview of the results of QuantiFERON-TB Gold (QFT) testing on uveitis patients in an interdisciplinary setting for a period of 3 years. Methods: Database search of all the patients tested for tuberculosis (Tb) with QFT. Results: Of 343 tested patients, overall 80 (23.3%) were positive and 253 (73.8%) negative (results were nonconclusive for 10 patients). Anatomic localization of the patients who tested positive were distributed (% of QFT+ tests) as anterior n=12 (15.0%), intermediate n=22 (27.5%), posterior n=26 (32.5%), and pan n=18 (22.5%). In 43 QFT+ patients we presumed a diagnosis of Tb due to additional clinical findings. Of these patients 16 were treated with full therapy following WHO recommendations. Conclusions: QFT testing gives surprisingly high numbers of positives in uveitis patients. This is not sufficiently explained by immigrant status of the patients. The frequency of positives is substantially higher than in other cohorts. This raises important questions regarding treatment implications. © 2014 Informa Healthcare USA, Inc.

Dapunt U.,University of Heidelberg | Spranger O.,University of Heidelberg | Gantz S.,University of Heidelberg | Burckhardt I.,Medical Microbiology and Hygiene | And 3 more authors.
Therapeutics and Clinical Risk Management | Year: 2015

Impaired fracture healing, especially when associated with bacterial infection, is a severe complication following long-bone fractures and requires special treatment. Because standard diagnostic techniques might provide falsely negative results, we evaluated the sonication method for detection of bacteria on implants of patients with fracture nonunions. A total of 49 patients with a nonunion (group NU) and, for comparison, 45 patients who had undergone routine removal of osteosynthetic material (group OM), were included in the study. Five different diagnostic methods (culture of tissue samples, culture of intraoperative swabs, histopathology of tissue samples, culture of sonication fluid, and 16S ribosomal DNA polymerase chain reaction of sonication fluid) were compared and related to clinical data. Among the diagnostic tests, culture of sonication fluid demonstrated by far the highest detection rate of bacteria (57%) in group NU, and rather unexpectedly 40% in group OM. Culture of sonication samples also revealed a broad spectrum of bacteria, in particular Propionibacterium spp. In conclusion, our results indicate that more bacteria can be detected on implants of patients with atrophic nonunions of long-bone fractures by means of the sonication procedure, which provides a valuable additional diagnostic tool to decide on a surgical procedure (eg, two-step procedure) and to further specify antimicrobial therapy. © 2015 Dapunt et al.

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