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Martini C.,University of Caen Lower Normandy | Martini C.,Catholic University of the Sacred Heart | Michaux C.,University of Caen Lower Normandy | Michaux C.,Institute for Molecular Infection Biology | And 10 more authors.
Infection and Immunity | Year: 2015

We previously showed that the mutant strain of Enterococcus faecalis lacking the transcriptional regulator SlyA is more virulent than the parental strain. We hypothesized that this phenotype was due to overexpression of the second gene of the slyA operon, ef_3001, renamed pmvE (for polyamine metabolism and virulence of E. faecalis). PmvE shares strong homologies with N1-spermidine/ spermine acetyltransferase enzymes involved in the metabolism of polyamines. In this study, we used an E. faecalis strain carrying the recombinant plasmid pMSP3535-pmvE (V19/p3535-pmvE), which allows the induction of pmvE by addition of nisin. Thereby, we showed that the overexpression of PmvE increased the virulence of E. faecalis in the Galleria mellonella infection model, as well as the persistence within peritoneal macrophages. We were also able to show a direct interaction between the His-tagged recombinant PmvE (rPmvE) protein and putrescine by the surface plasmon resonance (SPR) technique on a Biacore instrument. Moreover, biochemical assays showed that PmvE possesses an N-acetyltransferase activity toward polyamine substrates. Our results suggest that PmvE contributes to the virulence of E. faecalis, likely through its involvement in the polyamine metabolism. © 2015, American Society for Microbiology.

Bringmann G.,University of Wurzburg | Zhang G.,University of Wurzburg | Olschlager T.,Institute for Molecular Infection Biology | Stich A.,Medical Mission Institute | And 4 more authors.
Phytochemistry | Year: 2013

Naphthylisoquinoline alkaloids, named ancistectorine A1, N-methylancistectorine A1, ancistectorine A2, 5-epi-ancistectorine A2, ancistectorine A3, ancistectorine B1, and ancistectorine C1, have been isolated from twigs of the Chinese plant Ancistrocladus tectorius. The structural elucidation succeeded by chemical, spectroscopic, and chiroptical methods. Three of these compounds exhibited excellent, and specific, antiplasmodial activities, comparable with that of the as yet most active representative, dioncophylline C. Moreover, the antitumoral activities of two of the main alkaloids in this species was tested. © 2012 Elsevier Ltd. All rights reserved.

Balk A.,University of Wurzburg | Widmer T.,University of Wurzburg | Widmer T.,Novartis | Wiest J.,University of Wurzburg | And 10 more authors.
Pharmaceutical Research | Year: 2015

Purpose: A poorly water soluble acidic active pharmaceutical ingredient (API) was transformed into an ionic liquid (IL) aiming at faster and higher oral availability in comparison to a prodrug. Methods: API preparations were characterized in solid state by single crystal and powder diffraction, NMR, DSC, IR and in solution by NMR and ESI-MS. Dissolution and precipitation kinetics were detailed as was the role of the counterion on API supersaturation. Transepithelial API transport through Caco-2 monolayers and counterion cytotoxicity were assessed. Results: The mechanism leading to a 700 fold faster dissolution rate and longer duration of API supersaturation of the ionic liquid in comparison to the free acid was deciphered. Transepithelial transport was about three times higher for the IL in comparison to the prodrug when substances were applied as suspensions with the higher solubility of the IL outpacing the higher permeability of the prodrug. The counterion was nontoxic with IC50 values in the upper μM / lower mM range in cell lines of hepatic and renal origin as well as in macrophages. Conclusion: The IL approach was instrumental for tuning physico-chemical API properties, while avoiding the inherent need for structural changes as required for prodrugs. [Figure not available: see fulltext.] © 2014 Springer Science+Business Media New York.

Hartmann T.,Institute for Molecular Infection Biology | Dumig M.,Institute for Molecular Infection Biology | Jaber B.M.,University of Jordan | Szewczyk E.,Institute for Molecular Infection Biology | And 3 more authors.
Applied and Environmental Microbiology | Year: 2010

Recyclable markers based on site-specific recombination allow repetitive gene targeting in filamentous fungi. Here we describe for the first time functionality of the bacterial recombination system employing ß serine recombinase acting on six recognition sequences (β-rec/six) in a fungal host, the human pathogen Aspergillus fumigatus, and its use in establishing a self-excising resistance marker cassette for serial gene replacement. Copyright © 2020, American Society tor Microbiology. All Rights Reserved.

Nagel N.C.,Max Planck Institute for Chemical Ecology | Masic A.,Institute for Molecular Infection Biology | Schurigt U.,Institute for Molecular Infection Biology | Boland W.,Max Planck Institute for Chemical Ecology
Organic and Biomolecular Chemistry | Year: 2015

A flexible synthetic route to (R)-harmonine ((R)-1), the toxic principle of the Asian lady beetle Harmonia axyridis (H. axyridis), via reductive olefination of the macrocyclic lactone (S)-5, is reported. High enantiomeric purity is achieved by enantioselective saponification of the lactone rac-5 with horse liver esterase. Minor modifications in the synthetic route give access to racemic and chiral harmonine (1), analogs and putative biosynthetic precursors. In addition, the antimicrobial activity of harmonine against Leishmania major (L. major) is demonstrated and provides the rationale for harmonine-based drug development against parasitic diseases. This journal is © The Royal Society of Chemistry.2015.

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