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Haupt C.,University of Ulm | Thal D.R.,Universitatsklinikum Ulm | Horn U.,Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie | Fandrich M.,University of Ulm
BioSpektrum | Year: 2014

Conformational diseases, such as Alzheimer's or Parkinson's, are characterized by the misfolding of endogenous polypeptide chains into abnormal amyloid fibril conformations. To better analyze this process and its biological consequences and to generate tools for targeted interference in vitro and in vivo, we have biotechnologically generated a set of antibody fragments that are able to discriminate by binding between different amyloid assembly states. © 2014 Springer-Verlag Berlin Heidelberg. Literatur:.

Kampfer P.,Justus Liebig University | Lodders N.,Justus Liebig University | Martin K.,Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie | Avendano-Herrera R.,Andres Bello University
International Journal of Systematic and Evolutionary Microbiology | Year: 2012

Three Gram-staining-negative non-endospore-forming strains were isolated from farmed fish in Chile: one (LM-09-FpT) from a rainbow trout (Oncorhynchus mykiss) and the others (LM-19-FpTand LM-20-Fp) from two Atlantic salmon (Salmo salar). Phylogenetic analyses based on 16S rRNA gene sequences indicated that all three isolates belonged to the genus Flavobacterium. In these analyses, strain LM-09-FpTappeared most closely related to the type strains of Flavobacterium chungangense (98.5% sequence similarity), Flavobacterium glaciei (98.2 %), Flavobacterium aquidurense (97.6 %), Flavobacterium saccharophilum (97.6 %) and Flavobacterium hercynium (97.6 %). The 16S rRNA gene sequences of strains LM-19-FpTand LM-20-Fp were found to be identical and most similar to the corresponding sequences of the type strains of Flavobacterium aquidurense (98.6 %), Flavobacterium frigidimaris (98.5 %), Flavobacterium hercynium (97.9 %), Flavobacterium saccharophilum (97.7 %) and Flavobacterium pectinovorum (97.7 %). For each of the three novel strains, menaquinone (MK-6) was the predominant respiratory quinone and the major compounds in the polar lipid profile were phosphatidylethanolamine, an unidentified aminolipid, phosphatidylserine and two or three unknown lipids. The fatty acid profile of each strain, which comprised major amounts of iso-C15: 0, C15: 0and summed feature 3 (C16: 1ω7c and/or iso-C15: 02-OH) as well as smaller amounts of various hydroxylated fatty acids (e.g. iso-C16: 03-OH, iso-C17: 03-OH, C16: 03-OH and C15: 03- OH), indicated that each belonged to the genus Flavobacterium. Based on their physiological and biochemical characteristics and the results of DNA-DNA hybridizations, which showed relatively low levels of relatedness between the novel strains and the most closely related Flavobacterium species, strain LM-09-FpT(=LMG 26360T=CCM 7940T) represents a novel species within the genus Flavobacterium, for which the name Flavobacterium chilense sp. nov. is proposed, and strains LM-19-FpT(=LMG 26359T=CCM 7939T) and LM-20-Fp (=LMG 26331) represent a second novel species within the same genus, for which the name Flavobacterium araucananum sp. nov. is proposed. © 2012 IUMS.

Mayer K.,Universitatsklinikum Bonn | Hahn-Ast C.,Universitatsklinikum Bonn | Muckter S.,Universitatsklinikum Bonn | Schmitz A.,Universitatsklinikum Bonn | And 8 more authors.
Supportive Care in Cancer | Year: 2015

Purpose: Recent meta-analyses showed that antibiotic prophylaxis in patients with neutropenia after chemotherapy reduced the incidence of fever and mortality rate. Fluoroquinolones appear to be most effective and well tolerated. Thus, in April 2008, we changed our antibiotic prophylaxis regimen from cotrimoxazole/colistin (COT/COL) to the fluoroquinolone ciprofloxacin (CIP) in patients with acute myeloid leukemia (AML). The aim of this retrospective study was to compare efficacy and development of bacterial resistance with two different prophylaxis regimens over a time period of more than 4 years. Methods: Induction chemotherapy courses given for AML during the antibiotic prophylaxis period with COT/COL (01/2006-04/2008) and CIP (04/2008-06/2010) were retrospectively analyzed with a standard questionnaire. Results: Eighty-five courses in the COT/COL group and 105 in the CIP group were analyzed. The incidence of fever was not significantly different (COT/COL 80 % vs CIP 77 %; p = 0.724). Also, the rate of microbiologically documented infections was nearly the same (29 vs 26 %; p = 0.625). In addition, there was no significant difference in the incidence of clinically documented infections (11 vs 19 %; p = 0.155) or in the rates of detected gram-positive and gram-negative bacteria. Of note, there was no increase in resistance rates or cases with Clostridium difficile-associated diarrhea in the CIP group. Conclusion: The antibiotic prophylaxis with CIP compared to COT/COL in AML was similarly effective with no increase in bacterial resistance. COT/COL may have the advantages of providing additional prophylaxis against Pneumocystis jirovecii pneumonia and leaving fluoroquinolones as an additional option for treatment of febrile neutropenia. © 2015, Springer-Verlag Berlin Heidelberg.

Schrader F.C.,University of Marburg | Glinca S.,University of Marburg | Sattler J.M.,Universitatsklinikum Heidelberg | Dahse H..-M.,Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie | And 4 more authors.
ChemMedChem | Year: 2013

Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood- and pre-erythrocytic liver stages of the parasite. P.falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial typeII fatty acid biosynthesis (FASII). It has been shown to be essential for liver-stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood-stage parasite growth with IC50 values of 1.7 and 3.0μM and lead to a more prominent developmental attenuation of liver-stage parasites than the gold-standard drug, primaquine. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Busch B.,Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie | Ueberschaar N.,Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie | Behnken S.,Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie | Sugimoto Y.,Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie | And 5 more authors.
Angewandte Chemie - International Edition | Year: 2013

Freedom and control: First insights into the rare programmed iteration of an individual polyketide synthase (PKS) module were obtained from the analysis and mutation of aureothin (1) synthase. The first ketosynthase (KS) domain primes the PKS, allowing intermediate retrotransfer. Addition of a designated loading module results in a complete loss of iteration. The downstream KS functions as a gatekeeper for correct chain length. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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