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.
Hohenstein B.,Universitatsklinikum Carl Gustav Carus |
Licht C.,The Hospital for Sick Children |
Wiesener M.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Amann K.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 6 more authors.
Nephrologe | Year: 2015
Based on new pathophysiological discoveries in recent years, a new classification of glomerulonephritis with dominant or codominant C3 deposits was introduced in 2010, which represents the essential subgroup of C3 glomerulopathy (C3G). Although secondary causes can lead to immune complex-mediated membranoproliferative glomerulonephritis (MPGN), the major trigger of C3G is primarily dysregulation of the alternative complement pathway, which can often become apparent in the form of MPGN as well as various light microscopic phenotypes. Knowledge of the underlying pathophysiology of the disease is of high relevance for a subsequent differentiation after assessment of secondary causes. Initiation of a comprehensive analysis of complement factors, antibody screening and genetic analyses, should be part of a subsequent diagnostic work-up. Even though systematic evidence from studies is lacking, knowledge of the individual pathophysiology provides a robust foundation for the application of available therapeutic approaches for these often rapidly progressing forms of kidney disease, which frequently recur after kidney transplantation. This overview summarizes the current state of knowledge in the form of a (national German) expert consensus on the state of the art diagnostic work-up for C3 dominant glomerulonephritis and MPGN. © 2015, Springer-Verlag Berlin Heidelberg.
Influenza virus infections in patients with malignancies -- characteristics and outcome of the season 2014/15 A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO)
PubMed | Otto Von Guericke University of Magdeburg, University Hospital Jena, University of Cologne, Martin Luther University of Halle Wittenberg and 6 more.
Type: | Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology | Year: 2016
Influenza virus infections (IVI) may pose a vital threat to immunocompromised patients such as those suffering from malignancies, but specific data on epidemiology and outcome in these patients are scarce. In this study, we collected data on patients with active cancer or with a history of cancer, presenting with documented IVI in eight centres in Germany. Two hundred and three patients were identified, suffering from haematological malignancies or solid tumours; 109 (54%) patients had active malignant disease. Influenza A was detected in 155 (77%) and Influenza B in 46 (23%) of patients (genera not determined in two patients). Clinical symptoms were consistent with upper respiratory tract infection in 55/203 (27%), influenza-like illness in 82/203 (40%), and pneumonia in 67/203 (33%). Anti-viral treatment with oseltamivir was received by 116/195 (59%). Superinfections occurred in 37/203 (18%), and admission on an intensive care unit was required in 26/203 (13%). Seventeen patients (9%) died. Independent risk factors for death were delayed diagnosis of IVI and bacterial or fungal superinfection, but not underlying malignancy or ongoing immunosuppression. In conclusion, patients with IVI show high rates of pneumonia and mortality. Early and rapid diagnosis is essential. The high rate of pneumonia and superinfections should be taken into account when managing IVI in these patients.
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.
Leone M.R.,University of Naples Federico II |
Lackner G.,Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie |
Silipo A.,University of Naples Federico II |
Lanzetta R.,University of Naples Federico II |
And 3 more authors.
Angewandte Chemie - International Edition | Year: 2010
Dress code for living in a fungus: Analysis of the carbohydrate coating of the toxin-producing endobacterium of the phytopathogenic fungus Rhizopus microsporus revealed an unprecedented lipopolysaccharide (LPS) structure, which is important for infection and colonization of the fungal host. A mutant lacking the unusual [→2)-β-D-galactofuranose-(1→]n O antigen (red in the schematic illustration) was incapable of forming a stable symbiosis with the fungus. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
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.,Andrés 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.
Gerke J.,University of Gottingen |
Bayram O.,University of Gottingen |
Feussner K.,University of Gottingen |
Landesfeind M.,University of Gottingen |
And 3 more authors.
Applied and Environmental Microbiology | Year: 2012
The genomes of filamentous fungi comprise numerous putative gene clusters coding for the biosynthesis of chemically and structurally diverse secondary metabolites (SMs), which are rarely expressed under laboratory conditions. Previous approaches to activate these genes were based primarily on artificially targeting the cellular protein synthesis apparatus. Here, we applied an alternative approach of genetically impairing the protein degradation apparatus of the model fungus Aspergillus nidulans by deleting the conserved eukaryotic csnE/CSN5 deneddylase subunit of the COP9 signalosome. This defect in protein degradation results in the activation of a previously silenced gene cluster comprising a polyketide synthase gene producing the antibiotic 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde (DHMBA). The csnE/CSN5 gene is highly conserved in fungi, and therefore, the deletion is a feasible approach for the identification of new SMs. © 2012, American Society for Microbiology.
PubMed | Universitatsklinikum Jena, University of Leipzig and Leibniz Institute For Naturstoff Forschung Und Infektionsbiologie
Type: Journal Article | Journal: Infection | Year: 2016
Infections and subsequent septicemia are major complications in neutropenic patients with hematological malignancies. Here, we identify biomarker candidates for the early detection of an infectious origin, and monitoring of febrile neutropenia (FN).Proteome, metabolome, and conventional biomarkers from 20 patients with febrile neutropenia without proven infection (FNPI) were compared to 28 patients with proven infection, including 17 patients with bacteremia.Three peptides (mass to charge ratio 1017.4-1057.3; p-values 0.011-0.024), six proteins (mass to charge ratio 6881-17,215; p-values 0.002-0.004), and six phosphatidylcholines (p-values 0.007-0.037) were identified that differed in FNPI patients compared to patients with infection or bacteremia. Seven of these marker candidates discriminated FNPI from infection at fever onset with higher sensitivity and specificity (ROC-AUC 0.688-0.824) than conventional biomarkers i.e., procalcitonin, C-reactive protein, or interleukin-6 (ROC-AUC 0.535-0.672). In a post hoc analysis, monitoring the time course of four lysophosphatidylcholines, threonine, and tryptophan allowed for discrimination of patients with or without resolution of FN (ROC-AUC 0.648-0.919) with higher accuracy compared to conventional markers (ROC-AUC 0.514-0.871).Twenty-one promising biomarker candidates for the early detection of an infectious origin or for monitoring the course of FN were found which might overcome known shortcomings of conventional markers.