TY  - JOUR
A1  - Böhm, Lena
A1  - Torsin, Sanda
A1  - Tint, Su Hlaing
A1  - Eckstein, Marie Therese
A1  - Ludwig, Tobias
A1  - Pérez, J. Christian
T1  - The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice
JF  - PLoS Pathogens
N2  - Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators—ZCF8, ZFU2 and TRY4—and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms.
KW  - Candida albicans
KW  - deletion mutagenesis
KW  - gastrointestinal tract
KW  - fungi
KW  - regulator genes
KW  - gene regulation
KW  - mouse models
KW  - fungal genetics
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159120
VL  - 13
IS  - 10
ER  - 
TY  - JOUR
A1  - Schneider, Leon N.
A1  - Tanzer Krauel, Eva-Maria
A1  - Deutsch, Carl
A1  - Urbahns, Klaus
A1  - Bischof, Tobias
A1  - Maibom, Kristina A. M.
A1  - Landmann, Johannes
A1  - Keppner, Fabian
A1  - Kerpen, Christoph
A1  - Hailmann, Michael
A1  - Zapf, Ludwig
A1  - Knuplez, Tanja
A1  - Bertermann, Rüdiger
A1  - Ignat'ev, Nikolai V.
A1  - Finze, Maik
T1  - Stable and Storable N(CF\(_{3}\))\(_{2}\) Transfer Reagents
JF  - Chemistry—A European Journal
N2  - Fluorinated groups are essential for drug design, agrochemicals, and materials science. The bis(trifluoromethyl)amino group is an example of a stable group that has a high potential. While the number of molecules containing perfluoroalkyl, perfluoroalkoxy, and other fluorinated groups is steadily increasing, examples with the N(CF\(_{3}\))\(_{2}\) group are rare. One reason is that transfer reagents are scarce and metal-based storable reagents are unknown. Herein, a set of Cu\(^{I}\) and Ag\(^{I}\) bis(trifluoromethyl)amido complexes stabilized by N- and P-donor ligands with unprecedented stability are presented. The complexes are stable solids that can even be manipulated in air for a short time. They are bis(trifluoromethyl)amination reagents as shown by nucleophilic substitution and Sandmeyer reactions. In addition to a series of benzylbis(trifluoromethyl)amines, 2-bis(trifluoromethyl)amino acetate was obtained, which, upon hydrolysis, gives the fluorinated amino acid N,N-bis(trifluoromethyl)glycine.
KW  - silver
KW  - amination
KW  - copper
KW  - fluorinated ligands
KW  - N ligands
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256890
VL  - 27
IS  - 42
ER  - 
TY  - JOUR
A1  - Bruchhagen, Christin
A1  - Jarick, Marcel
A1  - Mewis, Carolin
A1  - Hertlein, Tobias
A1  - Niemann, Silke
A1  - Ohlsen, Knut
A1  - Peters, Georg
A1  - Planz, Oliver
A1  - Ludwig, Stephan
A1  - Ehrhardt, Christina
T1  - Metabolic conversion of CI-1040 turns a cellular MEK-inhibitor into an antibacterial compound
JF  - Scientific Reports
N2  - Influenza virus (IV) infections cause severe respiratory illnesses that can be complicated by bacterial super-infections. Previously, we identified the cellular Raf-MEK-ERK cascade as a promising antiviral target. Inhibitors of MEK, such as CI-1040, showed potent antiviral activity. However, it remained unclear if this inhibitor and its active form, ATR-002, might sensitize host cells to either IV or secondary bacterial infections. To address these questions, we studied the anti-pathogen activity of ATR-002 in comparison to CI-1040, particularly, its impact on Staphylococcus aureus (S. aureus), which is a major cause of IV super-infections. We analysed IV and S. aureus titres in vitro during super-infection in the presence and absence of the drugs and characterized the direct impact of ATR-002 on bacterial growth and phenotypic changes. Importantly, neither CI-1040 nor ATR-002 treatment led to increased bacterial titres during super-infection, indicating that the drug does not sensitize cells for bacterial infection. In contrast, we rather observed reduced bacterial titres in presence of ATR-002. Surprisingly, ATR-002 also led to reduced bacterial growth in suspension cultures, reduced stress- and antibiotic tolerance without resistance induction. Our data identified for the first time that a particular MEK-inhibitor metabolite exhibits direct antibacterial activity, which is likely due to interference with the bacterial PknB kinase/Stp phosphatase signalling system.
KW  - antimicrobials
KW  - pathogens
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221648
VL  - 8
ER  -