TY  - JOUR
A1  - Hempelmann, Alexander
A1  - Hartleb, Laura
A1  - van Straaten, Monique
A1  - Hashemi, Hamidreza
A1  - Zeelen, Johan P.
A1  - Bongers, Kevin
A1  - Papavasiliou, F. Nina
A1  - Engstler, Markus
A1  - Stebbins, C. Erec
A1  - Jones, Nicola G.
T1  - Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome
JF  - Cell Reports
N2  - The dense variant surface glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host’s antibody response. To explore the epitope space of VSGs, we generate anti-VSG nanobodies and combine high-resolution structural analysis of VSG-nanobody complexes with binding assays on living cells, revealing that these camelid antibodies bind deeply inside the coat. One nanobody causes rapid loss of cellular motility, possibly due to blockage of VSG mobility on the coat, whose rapid endocytosis and exocytosis are mechanistically linked to Trypanosoma brucei propulsion and whose density is required for survival. Electron microscopy studies demonstrate that this loss of motility is accompanied by rapid formation and shedding of nanovesicles and nanotubes, suggesting that increased protein crowding on the dense membrane can be a driving force for membrane fission in living cells.
KW  - African trypanosome
KW  - host-pathogen interaction
KW  - variant surface glycoproteins
KW  - immune epitope mapping
KW  - structural biology
KW  - nanovesicle formation
KW  - nanotube formation
KW  - protein crowding
KW  - membrane fission
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270285
VL  - 37
IS  - 5
ER  - 
TY  - JOUR
A1  - Kunz, Tobias C.
A1  - Rühling, Marcel
A1  - Moldovan, Adriana
A1  - Paprotka, Kerstin
A1  - Kozjak-Pavlovic, Vera
A1  - Rudel, Thomas
A1  - Fraunholz, Martin
T1  - The Expandables: Cracking the Staphylococcal Cell Wall for Expansion Microscopy
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Expansion Microscopy (ExM) is a novel tool improving the resolution of fluorescence microscopy by linking the sample into a hydrogel that gets physically expanded in water. Previously, we have used ExM to visualize the intracellular Gram-negative pathogens Chlamydia trachomatis, Simkania negevensis, and Neisseria gonorrhoeae. Gram-positive bacteria have a rigid and thick cell wall that impedes classic expansion strategies. Here we developed an approach, which included a series of enzymatic treatments resulting in isotropic 4× expansion of the Gram-positive pathogen Staphylococcus aureus. We further demonstrate the suitability of the technique for imaging of planktonic bacteria as well as endocytosed, intracellular bacteria at a spatial resolution of approximately 60 nm with conventional confocal laser scanning microscopy.
KW  - high-resolution imaging
KW  - endosomes
KW  - autophagosomes
KW  - host-pathogen interaction
KW  - expansion microscopy
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232292
SN  - 2235-2988
VL  - 11
ER  - 
TY  - JOUR
A1  - Dühring, Sybille
A1  - Germerodt, Sebastian
A1  - Skerka, Christine
A1  - Zipfel, Peter F.
A1  - Dandekar, Thomas
A1  - Schuster, Stefan
T1  - Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies
JF  - Frontiers in Microbiology
N2  - The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given.
KW  - agent-based model
KW  - antimicrobial peptides
KW  - fungal pathogens
KW  - Candida albicans
KW  - immunological cross-talk
KW  - beta-lactamase inhibition
KW  - in vitro
KW  - biomaterial surfaces
KW  - biofilm formation
KW  - dendritic cells
KW  - infection
KW  - resistance
KW  - human immune system
KW  - host-pathogen interaction
KW  - computational systems biology
KW  - defense and evasion strategies
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151621
VL  - 6
IS  - 625
ER  -