---
_id: '803'
abstract:
- lang: eng
  text: Eukaryotic cells store their chromosomes in a single nucleus. This is important
    to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei)
    are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble
    their nucleus and release individualized chromosomes for segregation. How numerous
    chromosomes subsequently reform a single nucleus has remained unclear. Using image-based
    screening of human cells, we identified barrier-to-autointegration factor (BAF)
    as a key factor guiding membranes to form a single nucleus. Unexpectedly, nuclear
    assembly does not require BAF?s association with inner nuclear membrane proteins
    but instead relies on BAF?s ability to bridge distant DNA sites. Live-cell imaging
    and in vitro reconstitution showed that BAF enriches around the mitotic chromosome
    ensemble to induce a densely cross-bridged chromatin layer that is mechanically
    stiff and limits membranes to the surface. Our study reveals that BAF-mediated
    changes in chromosome mechanics underlie nuclear assembly with broad implications
    for proper genome function.
acknowledged_ssus:
- _id: Bio
article_processing_charge: No
author:
- first_name: Matthias
  full_name: Samwer, Matthias
  last_name: Samwer
- first_name: Maximilian
  full_name: Schneider, Maximilian
  last_name: Schneider
- first_name: Rudolf
  full_name: Hoefler, Rudolf
  last_name: Hoefler
- first_name: Philipp S
  full_name: Schmalhorst, Philipp S
  id: 309D50DA-F248-11E8-B48F-1D18A9856A87
  last_name: Schmalhorst
  orcid: 0000-0002-5795-0133
- first_name: Julian
  full_name: Jude, Julian
  last_name: Jude
- first_name: Johannes
  full_name: Zuber, Johannes
  last_name: Zuber
- first_name: Daniel
  full_name: Gerlic, Daniel
  last_name: Gerlic
citation:
  ama: Samwer M, Schneider M, Hoefler R, et al. DNA cross-bridging shapes a single
    nucleus from a set of mitotic chromosomes. <i>Cell</i>. 2017;170(5):956-972. doi:<a
    href="https://doi.org/10.1016/j.cell.2017.07.038">10.1016/j.cell.2017.07.038</a>
  apa: Samwer, M., Schneider, M., Hoefler, R., Schmalhorst, P. S., Jude, J., Zuber,
    J., &#38; Gerlic, D. (2017). DNA cross-bridging shapes a single nucleus from a
    set of mitotic chromosomes. <i>Cell</i>. Cell Press. <a href="https://doi.org/10.1016/j.cell.2017.07.038">https://doi.org/10.1016/j.cell.2017.07.038</a>
  chicago: Samwer, Matthias, Maximilian Schneider, Rudolf Hoefler, Philipp S Schmalhorst,
    Julian Jude, Johannes Zuber, and Daniel Gerlic. “DNA Cross-Bridging Shapes a Single
    Nucleus from a Set of Mitotic Chromosomes.” <i>Cell</i>. Cell Press, 2017. <a
    href="https://doi.org/10.1016/j.cell.2017.07.038">https://doi.org/10.1016/j.cell.2017.07.038</a>.
  ieee: M. Samwer <i>et al.</i>, “DNA cross-bridging shapes a single nucleus from
    a set of mitotic chromosomes,” <i>Cell</i>, vol. 170, no. 5. Cell Press, pp. 956–972,
    2017.
  ista: Samwer M, Schneider M, Hoefler R, Schmalhorst PS, Jude J, Zuber J, Gerlic
    D. 2017. DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes.
    Cell. 170(5), 956–972.
  mla: Samwer, Matthias, et al. “DNA Cross-Bridging Shapes a Single Nucleus from a
    Set of Mitotic Chromosomes.” <i>Cell</i>, vol. 170, no. 5, Cell Press, 2017, pp.
    956–72, doi:<a href="https://doi.org/10.1016/j.cell.2017.07.038">10.1016/j.cell.2017.07.038</a>.
  short: M. Samwer, M. Schneider, R. Hoefler, P.S. Schmalhorst, J. Jude, J. Zuber,
    D. Gerlic, Cell 170 (2017) 956–972.
date_created: 2018-12-11T11:48:35Z
date_published: 2017-08-24T00:00:00Z
date_updated: 2023-09-27T10:59:14Z
day: '24'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.1016/j.cell.2017.07.038
external_id:
  isi:
  - '000408372400014'
file:
- access_level: open_access
  checksum: 64897b0c5373f22273f598e4672c60ff
  content_type: application/pdf
  creator: dernst
  date_created: 2019-01-18T13:45:40Z
  date_updated: 2020-07-14T12:48:08Z
  file_id: '5852'
  file_name: 2017_Cell_Samwer.pdf
  file_size: 17666637
  relation: main_file
file_date_updated: 2020-07-14T12:48:08Z
has_accepted_license: '1'
intvolume: '       170'
isi: 1
issue: '5'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 956 - 972
publication: Cell
publication_identifier:
  issn:
  - '00928674'
publication_status: published
publisher: Cell Press
publist_id: '6848'
quality_controlled: '1'
scopus_import: '1'
status: public
title: DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 170
year: '2017'
...
---
_id: '804'
abstract:
- lang: eng
  text: Polysaccharides (carbohydrates) are key regulators of a large number of cell
    biological processes. However, precise biochemical or genetic manipulation of
    these often complex structures is laborious and hampers experimental structure–function
    studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool
    to generate and test hypotheses on saccharide function. Yet, currently used MD
    force fields often overestimate the aggregation propensity of polysaccharides,
    affecting the usability of those simulations. Here we tested MARTINI, a popular
    coarse-grained (CG) force field for biological macromolecules, for its ability
    to accurately represent molecular forces between saccharides. To this end, we
    calculated a thermodynamic solution property, the second virial coefficient of
    the osmotic pressure (B22). Comparison with light scattering experiments revealed
    a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing
    at an imbalance of the nonbonded solute–solute, solute–water, and water–water
    interactions. This finding also applies to smaller oligosaccharides which were
    all found to aggregate in simulations even at moderate concentrations, well below
    their solubility limit. Finally, we explored the influence of the Lennard-Jones
    (LJ) interaction between saccharide molecules and propose a simple scaling of
    the LJ interaction strength that makes MARTINI more reliable for the simulation
    of saccharides.
acknowledged_ssus:
- _id: ScienComp
acknowledgement: P.S.S. was supported by research fellowship 2811/1-1 from the German
  Research Foundation (DFG), and M.S. was supported by EMBO Long Term Fellowship ALTF
  187-2013 and Grant GC65-32 from the  Interdisciplinary Centre for Mathematical and
  Computational Modelling (ICM), University of Warsaw, Poland. The authors thank Antje
  Potthast, Marek Cieplak, Tomasz Włodarski, and Damien Thompson for fruitful discussions
  and the IST Austria Scientific Computing Facility for support.
article_processing_charge: No
author:
- first_name: Philipp S
  full_name: Schmalhorst, Philipp S
  id: 309D50DA-F248-11E8-B48F-1D18A9856A87
  last_name: Schmalhorst
  orcid: 0000-0002-5795-0133
- first_name: Felix
  full_name: Deluweit, Felix
  last_name: Deluweit
- first_name: Roger
  full_name: Scherrers, Roger
  last_name: Scherrers
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
- first_name: Mateusz K
  full_name: Sikora, Mateusz K
  id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87
  last_name: Sikora
citation:
  ama: Schmalhorst PS, Deluweit F, Scherrers R, Heisenberg C-PJ, Sikora MK. Overcoming
    the limitations of the MARTINI force field in simulations of polysaccharides.
    <i>Journal of Chemical Theory and Computation</i>. 2017;13(10):5039-5053. doi:<a
    href="https://doi.org/10.1021/acs.jctc.7b00374">10.1021/acs.jctc.7b00374</a>
  apa: Schmalhorst, P. S., Deluweit, F., Scherrers, R., Heisenberg, C.-P. J., &#38;
    Sikora, M. K. (2017). Overcoming the limitations of the MARTINI force field in
    simulations of polysaccharides. <i>Journal of Chemical Theory and Computation</i>.
    American Chemical Society. <a href="https://doi.org/10.1021/acs.jctc.7b00374">https://doi.org/10.1021/acs.jctc.7b00374</a>
  chicago: Schmalhorst, Philipp S, Felix Deluweit, Roger Scherrers, Carl-Philipp J
    Heisenberg, and Mateusz K Sikora. “Overcoming the Limitations of the MARTINI Force
    Field in Simulations of Polysaccharides.” <i>Journal of Chemical Theory and Computation</i>.
    American Chemical Society, 2017. <a href="https://doi.org/10.1021/acs.jctc.7b00374">https://doi.org/10.1021/acs.jctc.7b00374</a>.
  ieee: P. S. Schmalhorst, F. Deluweit, R. Scherrers, C.-P. J. Heisenberg, and M.
    K. Sikora, “Overcoming the limitations of the MARTINI force field in simulations
    of polysaccharides,” <i>Journal of Chemical Theory and Computation</i>, vol. 13,
    no. 10. American Chemical Society, pp. 5039–5053, 2017.
  ista: Schmalhorst PS, Deluweit F, Scherrers R, Heisenberg C-PJ, Sikora MK. 2017.
    Overcoming the limitations of the MARTINI force field in simulations of polysaccharides.
    Journal of Chemical Theory and Computation. 13(10), 5039–5053.
  mla: Schmalhorst, Philipp S., et al. “Overcoming the Limitations of the MARTINI
    Force Field in Simulations of Polysaccharides.” <i>Journal of Chemical Theory
    and Computation</i>, vol. 13, no. 10, American Chemical Society, 2017, pp. 5039–53,
    doi:<a href="https://doi.org/10.1021/acs.jctc.7b00374">10.1021/acs.jctc.7b00374</a>.
  short: P.S. Schmalhorst, F. Deluweit, R. Scherrers, C.-P.J. Heisenberg, M.K. Sikora,
    Journal of Chemical Theory and Computation 13 (2017) 5039–5053.
date_created: 2018-12-11T11:48:35Z
date_published: 2017-10-10T00:00:00Z
date_updated: 2023-09-27T10:58:45Z
day: '10'
department:
- _id: CaHe
doi: 10.1021/acs.jctc.7b00374
external_id:
  isi:
  - '000412965700036'
intvolume: '        13'
isi: 1
issue: '10'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://arxiv.org/abs/1704.03773
month: '10'
oa: 1
oa_version: Submitted Version
page: 5039 - 5053
publication: Journal of Chemical Theory and Computation
publication_identifier:
  issn:
  - '15499618'
publication_status: published
publisher: American Chemical Society
publist_id: '6847'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Overcoming the limitations of the MARTINI force field in simulations of polysaccharides
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 13
year: '2017'
...
---
_id: '802'
abstract:
- lang: eng
  text: Glycoinositolphosphoceramides (GIPCs) are complex sphingolipids present at
    the plasma membrane of various eukaryotes with the important exception of mammals.
    In fungi, these glycosphingolipids commonly contain an alpha-mannose residue (Man)
    linked at position 2 of the inositol. However, several pathogenic fungi additionally
    synthesize zwitterionic GIPCs carrying an alpha-glucosamine residue (GlcN) at
    this position. In the human pathogen Aspergillus fumigatus, the GlcNalpha1,2IPC
    core (where IPC is inositolphosphoceramide) is elongated to Manalpha1,3Manalpha1,6GlcNalpha1,2IPC,
    which is the most abundant GIPC synthesized by this fungus. In this study, we
    identified an A. fumigatus N-acetylglucosaminyltransferase, named GntA, and demonstrate
    its involvement in the initiation of zwitterionic GIPC biosynthesis. Targeted
    deletion of the gene encoding GntA in A. fumigatus resulted in complete absence
    of zwitterionic GIPC; a phenotype that could be reverted by episomal expression
    of GntA in the mutant. The N-acetylhexosaminyltransferase activity of GntA was
    substantiated by production of N-acetylhexosamine-IPC in the yeast Saccharomyces
    cerevisiae upon GntA expression. Using an in vitro assay, GntA was furthermore
    shown to use UDP-N-acetylglucosamine as donor substrate to generate a glycolipid
    product resistant to saponification and to digestion by phosphatidylinositol-phospholipase
    C as expected for GlcNAcalpha1,2IPC. Finally, as the enzymes involved in mannosylation
    of IPC, GntA was localized to the Golgi apparatus, the site of IPC synthesis.
author:
- first_name: Jakob
  full_name: Engel, Jakob
  last_name: Engel
- first_name: Philipp S
  full_name: Schmalhorst, Philipp S
  id: 309D50DA-F248-11E8-B48F-1D18A9856A87
  last_name: Schmalhorst
  orcid: 0000-0002-5795-0133
- first_name: Anke
  full_name: Kruger, Anke
  last_name: Kruger
- first_name: Christina
  full_name: Muller, Christina
  last_name: Muller
- first_name: Falk
  full_name: Buettner, Falk
  last_name: Buettner
- first_name: Françoise
  full_name: Routier, Françoise
  last_name: Routier
citation:
  ama: Engel J, Schmalhorst PS, Kruger A, Muller C, Buettner F, Routier F. Characterization
    of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic
    glycoinositolphosphoceramide biosynthesis. <i>Glycobiology</i>. 2015;25(12):1423-1430.
    doi:<a href="https://doi.org/10.1093/glycob/cwv059">10.1093/glycob/cwv059</a>
  apa: Engel, J., Schmalhorst, P. S., Kruger, A., Muller, C., Buettner, F., &#38;
    Routier, F. (2015). Characterization of an N-acetylglucosaminyltransferase involved
    in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis.
    <i>Glycobiology</i>. Oxford University Press. <a href="https://doi.org/10.1093/glycob/cwv059">https://doi.org/10.1093/glycob/cwv059</a>
  chicago: Engel, Jakob, Philipp S Schmalhorst, Anke Kruger, Christina Muller, Falk
    Buettner, and Françoise Routier. “Characterization of an N-Acetylglucosaminyltransferase
    Involved in Aspergillus Fumigatus Zwitterionic Glycoinositolphosphoceramide Biosynthesis.”
    <i>Glycobiology</i>. Oxford University Press, 2015. <a href="https://doi.org/10.1093/glycob/cwv059">https://doi.org/10.1093/glycob/cwv059</a>.
  ieee: J. Engel, P. S. Schmalhorst, A. Kruger, C. Muller, F. Buettner, and F. Routier,
    “Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus
    fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis,” <i>Glycobiology</i>,
    vol. 25, no. 12. Oxford University Press, pp. 1423–1430, 2015.
  ista: Engel J, Schmalhorst PS, Kruger A, Muller C, Buettner F, Routier F. 2015.
    Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus
    fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis. Glycobiology.
    25(12), 1423–1430.
  mla: Engel, Jakob, et al. “Characterization of an N-Acetylglucosaminyltransferase
    Involved in Aspergillus Fumigatus Zwitterionic Glycoinositolphosphoceramide Biosynthesis.”
    <i>Glycobiology</i>, vol. 25, no. 12, Oxford University Press, 2015, pp. 1423–30,
    doi:<a href="https://doi.org/10.1093/glycob/cwv059">10.1093/glycob/cwv059</a>.
  short: J. Engel, P.S. Schmalhorst, A. Kruger, C. Muller, F. Buettner, F. Routier,
    Glycobiology 25 (2015) 1423–1430.
date_created: 2018-12-11T11:48:35Z
date_published: 2015-12-01T00:00:00Z
date_updated: 2021-01-12T08:16:33Z
day: '01'
department:
- _id: CaHe
doi: 10.1093/glycob/cwv059
external_id:
  pmid:
  - '26306635'
intvolume: '        25'
issue: '12'
language:
- iso: eng
month: '12'
oa_version: None
page: 1423 - 1430
pmid: 1
publication: Glycobiology
publication_status: published
publisher: Oxford University Press
publist_id: '6851'
quality_controlled: '1'
scopus_import: 1
status: public
title: Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus
  fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 25
year: '2015'
...
---
_id: '801'
abstract:
- lang: eng
  text: Fungal cell walls frequently contain a polymer of mannose and galactose called
    galactomannan. In the pathogenic filamentous fungus Aspergillus fumigatus, this
    polysaccharide is made of a linear mannan backbone with side chains of galactofuran
    and is anchored to the plasma membrane via a glycosylphosphatidylinositol or is
    covalently linked to the cell wall. To date, the biosynthesis and significance
    of this polysaccharide are unknown. The present data demonstrate that deletion
    of the Golgi UDP-galactofuranose transporter GlfB or the GDP-mannose transporter
    GmtA leads to the absence of galactofuran or galactomannan, respectively. This
    indicates that the biosynthesis of galactomannan probably occurs in the lumen
    of the Golgi apparatus and thus contrasts with the biosynthesis of other fungal
    cell wall polysaccharides studied to date that takes place at the plasma membrane.
    Transglycosylation of galactomannan from the membrane to the cell wall is hypothesized
    because both the cell wall-bound and membrane-bound polysaccharide forms are affected
    in the generated mutants. Considering the severe growth defect of the A. fumigatus
    GmtA-deficient mutant, proving this paradigm might provide new targets for antifungal
    therapy.
acknowledgement: This work was supported by the Deutsche Forschungsgemeinschaft.
article_processing_charge: No
article_type: original
author:
- first_name: Jakob
  full_name: Engel, Jakob
  last_name: Engel
- first_name: Philipp S
  full_name: Schmalhorst, Philipp S
  id: 309D50DA-F248-11E8-B48F-1D18A9856A87
  last_name: Schmalhorst
  orcid: 0000-0002-5795-0133
- first_name: Françoise
  full_name: Routier, Françoise
  last_name: Routier
citation:
  ama: Engel J, Schmalhorst PS, Routier F. Biosynthesis of the fungal cell wall polysaccharide
    galactomannan requires intraluminal GDP-mannose. <i>Journal of Biological Chemistry</i>.
    2012;287(53):44418-44424. doi:<a href="https://doi.org/10.1074/jbc.M112.398321">10.1074/jbc.M112.398321</a>
  apa: Engel, J., Schmalhorst, P. S., &#38; Routier, F. (2012). Biosynthesis of the
    fungal cell wall polysaccharide galactomannan requires intraluminal GDP-mannose.
    <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and
    Molecular Biology. <a href="https://doi.org/10.1074/jbc.M112.398321">https://doi.org/10.1074/jbc.M112.398321</a>
  chicago: Engel, Jakob, Philipp S Schmalhorst, and Françoise Routier. “Biosynthesis
    of the Fungal Cell Wall Polysaccharide Galactomannan Requires Intraluminal GDP-Mannose.”
    <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and
    Molecular Biology, 2012. <a href="https://doi.org/10.1074/jbc.M112.398321">https://doi.org/10.1074/jbc.M112.398321</a>.
  ieee: J. Engel, P. S. Schmalhorst, and F. Routier, “Biosynthesis of the fungal cell
    wall polysaccharide galactomannan requires intraluminal GDP-mannose,” <i>Journal
    of Biological Chemistry</i>, vol. 287, no. 53. American Society for Biochemistry
    and Molecular Biology, pp. 44418–44424, 2012.
  ista: Engel J, Schmalhorst PS, Routier F. 2012. Biosynthesis of the fungal cell
    wall polysaccharide galactomannan requires intraluminal GDP-mannose. Journal of
    Biological Chemistry. 287(53), 44418–44424.
  mla: Engel, Jakob, et al. “Biosynthesis of the Fungal Cell Wall Polysaccharide Galactomannan
    Requires Intraluminal GDP-Mannose.” <i>Journal of Biological Chemistry</i>, vol.
    287, no. 53, American Society for Biochemistry and Molecular Biology, 2012, pp.
    44418–24, doi:<a href="https://doi.org/10.1074/jbc.M112.398321">10.1074/jbc.M112.398321</a>.
  short: J. Engel, P.S. Schmalhorst, F. Routier, Journal of Biological Chemistry 287
    (2012) 44418–44424.
date_created: 2018-12-11T11:48:34Z
date_published: 2012-12-28T00:00:00Z
date_updated: 2022-03-21T07:57:14Z
day: '28'
doi: 10.1074/jbc.M112.398321
extern: '1'
external_id:
  pmid:
  - '23139423'
intvolume: '       287'
issue: '53'
language:
- iso: eng
month: '12'
oa_version: None
page: 44418 - 44424
pmid: 1
publication: Journal of Biological Chemistry
publication_status: published
publisher: American Society for Biochemistry and Molecular Biology
publist_id: '6852'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Biosynthesis of the fungal cell wall polysaccharide galactomannan requires
  intraluminal GDP-mannose
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 287
year: '2012'
...
---
_id: '3292'
abstract:
- lang: eng
  text: Galactofuranose (Galf) containing molecules have been described at the cell
    surface of several eukaryotes and shown to contribute to the virulence of the
    parasite Leishmania major and the fungus Aspergillus fumigatus. It is anticipated
    that a number of the surface glycoconjugates such as N-glycans or glycolipids
    are galactofuranosylated in the Golgi apparatus. This raises the question of how
    the substrate for galactofuranosylation reactions, UDP-Galf, which is synthesized
    in the cytosol, translocates into the organelles of the secretory pathway. Here
    we report the first identification of a Golgi-localized nucleotide sugar transporter,
    named GlfB, with specificity for a UDP-Galf. In vitro transport assays established
    binding of UDP-Galf to GlfB and excluded transport of several other nucleotide
    sugars. Furthermore, the implication of glfB in the galactofuranosylation of A.
    fumigatus glycoconjugates and galactomannan was demonstrated by a targeted gene
    deletion approach. Our data reveal a direct connection between galactomannan and
    the organelles of the secretory pathway that strongly suggests that the cell wall-bound
    polysaccharide originates from its glycosylphosphatidylinositol-anchored form.
author:
- first_name: Jakob
  full_name: Engel, Jakob
  last_name: Engel
- first_name: Philipp S
  full_name: Schmalhorst, Philipp S
  id: 309D50DA-F248-11E8-B48F-1D18A9856A87
  last_name: Schmalhorst
  orcid: 0000-0002-5795-0133
- first_name: Thilo
  full_name: Dörk Bousset, Thilo
  last_name: Dörk Bousset
- first_name: Vincent
  full_name: Ferrières, Vincent
  last_name: Ferrières
- first_name: Françoise
  full_name: Routier, Françoise
  last_name: Routier
citation:
  ama: Engel J, Schmalhorst PS, Dörk Bousset T, Ferrières V, Routier F. A single UDP
    galactofuranose transporter is required for galactofuranosylation in Aspergillus
    fumigatus. <i>Journal of Biological Chemistry</i>. 2009;284(49):33859-33868. doi:<a
    href="https://doi.org/10.1074/jbc.M109.070219 ">10.1074/jbc.M109.070219 </a>
  apa: Engel, J., Schmalhorst, P. S., Dörk Bousset, T., Ferrières, V., &#38; Routier,
    F. (2009). A single UDP galactofuranose transporter is required for galactofuranosylation
    in Aspergillus fumigatus. <i>Journal of Biological Chemistry</i>. American Society
    for Biochemistry and Molecular Biology. <a href="https://doi.org/10.1074/jbc.M109.070219
    ">https://doi.org/10.1074/jbc.M109.070219 </a>
  chicago: Engel, Jakob, Philipp S Schmalhorst, Thilo Dörk Bousset, Vincent Ferrières,
    and Françoise Routier. “A Single UDP Galactofuranose Transporter Is Required for
    Galactofuranosylation in Aspergillus Fumigatus.” <i>Journal of Biological Chemistry</i>.
    American Society for Biochemistry and Molecular Biology, 2009. <a href="https://doi.org/10.1074/jbc.M109.070219
    ">https://doi.org/10.1074/jbc.M109.070219 </a>.
  ieee: J. Engel, P. S. Schmalhorst, T. Dörk Bousset, V. Ferrières, and F. Routier,
    “A single UDP galactofuranose transporter is required for galactofuranosylation
    in Aspergillus fumigatus,” <i>Journal of Biological Chemistry</i>, vol. 284, no.
    49. American Society for Biochemistry and Molecular Biology, pp. 33859–33868,
    2009.
  ista: Engel J, Schmalhorst PS, Dörk Bousset T, Ferrières V, Routier F. 2009. A single
    UDP galactofuranose transporter is required for galactofuranosylation in Aspergillus
    fumigatus. Journal of Biological Chemistry. 284(49), 33859–33868.
  mla: Engel, Jakob, et al. “A Single UDP Galactofuranose Transporter Is Required
    for Galactofuranosylation in Aspergillus Fumigatus.” <i>Journal of Biological
    Chemistry</i>, vol. 284, no. 49, American Society for Biochemistry and Molecular
    Biology, 2009, pp. 33859–68, doi:<a href="https://doi.org/10.1074/jbc.M109.070219
    ">10.1074/jbc.M109.070219 </a>.
  short: J. Engel, P.S. Schmalhorst, T. Dörk Bousset, V. Ferrières, F. Routier, Journal
    of Biological Chemistry 284 (2009) 33859–33868.
date_created: 2018-12-11T12:02:30Z
date_published: 2009-12-04T00:00:00Z
date_updated: 2021-01-12T07:42:26Z
day: '04'
doi: '10.1074/jbc.M109.070219 '
extern: '1'
intvolume: '       284'
issue: '49'
language:
- iso: eng
month: '12'
oa_version: None
page: 33859 - 33868
publication: Journal of Biological Chemistry
publication_status: published
publisher: American Society for Biochemistry and Molecular Biology
publist_id: '3353'
quality_controlled: '1'
status: public
title: A single UDP galactofuranose transporter is required for galactofuranosylation
  in Aspergillus fumigatus
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 284
year: '2009'
...
---
_id: '3400'
abstract:
- lang: eng
  text: |-
    Invasive fungal infections pose a serious threat to immunocompromised people. Most of these infections are caused by either Candida or Aspergillus species, with A. fumigatus being the predominant causative agent of Invasive Aspergillosis. Affected people comprise mainly haematopoietic stem cell or solid organ transplant patients who receive either high-dose corticosteroids or immunosuppressants. These risk factors predispose to the development of Invasive
    Aspergillosis which is lethal in 20 to 80 % of the cases, largely due to insufficient efficacy of current antifungal therapy. Thus one major aim in current mycological research is the identification of new drug targets.
    The polysaccharide-based fungal cell wall is both essential to fungi and absent from human cells which makes it appear an attractive new target. Notably, many components of the A. fumigatus cell wall, including the polysaccharide galactomannan, glycoproteins, and glycolipids, contain the unusual sugar galactofuranose (Galf). In contrast to the other cell wall monosaccharides, Galf does not occur on human cells but is known as component of cell surface molecules of many pathogenic bacteria and protozoa, such as Mycobacterium tuberculosis or Leishmania major. These molecules are often essential for virulence or viability of these organisms which suggested a possible role of Galf in the pathogenicity of A. fumigatus.
    To address the importance of Galf in A. fumigatus, the key biosynthesis gene glfA, encoding UDPgalactopyranose mutase (UGM), was deleted. In different experimental approaches it was demonstrated that the absence of the glfA gene led to a complete loss of Galf-containing glycans.
    Analysis of the DeltaglfA phenotype revealed growth and sporulation defects, reduced thermotolerance and an increased susceptibility to antifungal drugs. Electron Microscopy indicated a cell wall defect as a likely cause for the observed impairments. Furthermore, the virulence of the DeltaglfA mutant was found to be severely attenuated in a murine model of Invasive Aspergillosis.
    The second focus of this study was laid on further elucidation of the galactofuranosylation pathway in A. fumigatus. In eukaryotes, a UDP-Galf transporter is likely required to transport UDP-Galf from the
    cytosol into the organelles of the secretory pathway, but no such activity had been described. Sixteen candidate genes were identified in the A. fumigatus genome of which one, glfB, was found in close proximity to the glfA gene. In vitro transport assays revealed specificity of GlfB for UDP-Galf suggesting that glfB encoded indeed a UDP-Galf transporter. The influence of glfB on
    galactofuranosylation was determined by a DeltaglfB deletion mutant, which closely recapitulated the DeltaglfA phenotype and was likewise found to be completely devoid of Galf. It could be concluded that all galactofuranosylation processes in A. fumigatus occur in the secretory pathway, including the biosynthesis of the cell wall polysaccharide galactomannan whose subcellular origin was previously disputed.

    Thus in the course of this study the first UDP-Galf specific nucleotide sugar transporter was identified and its requirement for galactofuranosylation in A. fumigatus demonstrated. Moreover, it was shown that blocking the galactofuranosylation pathway impaired virulence of A. fumigatus which suggests the UDP-Galf biosynthesis enzyme UGM as a target for new antifungal drugs.
author:
- first_name: Philipp S
  full_name: Philipp Schmalhorst
  id: 309D50DA-F248-11E8-B48F-1D18A9856A87
  last_name: Schmalhorst
  orcid: 0000-0002-5795-0133
citation:
  ama: Schmalhorst PS. Biosynthesis of Galactofuranose Containing Glycans and Their
    Relevance for the Pathogenic Fungus Aspergillus fumigatus. 2009:1-72.
  apa: Schmalhorst, P. S. (2009). <i>Biosynthesis of Galactofuranose Containing Glycans
    and Their Relevance for the Pathogenic Fungus Aspergillus fumigatus</i>. Gottfried
    Wilhelm Leibniz Universität Hannover.
  chicago: Schmalhorst, Philipp S. “Biosynthesis of Galactofuranose Containing Glycans
    and Their Relevance for the Pathogenic Fungus Aspergillus Fumigatus.” Gottfried
    Wilhelm Leibniz Universität Hannover, 2009.
  ieee: P. S. Schmalhorst, “Biosynthesis of Galactofuranose Containing Glycans and
    Their Relevance for the Pathogenic Fungus Aspergillus fumigatus,” Gottfried Wilhelm
    Leibniz Universität Hannover, 2009.
  ista: Schmalhorst PS. 2009. Biosynthesis of Galactofuranose Containing Glycans and
    Their Relevance for the Pathogenic Fungus Aspergillus fumigatus. Gottfried Wilhelm
    Leibniz Universität Hannover.
  mla: Schmalhorst, Philipp S. <i>Biosynthesis of Galactofuranose Containing Glycans
    and Their Relevance for the Pathogenic Fungus Aspergillus Fumigatus</i>. Gottfried
    Wilhelm Leibniz Universität Hannover, 2009, pp. 1–72.
  short: P.S. Schmalhorst, Biosynthesis of Galactofuranose Containing Glycans and
    Their Relevance for the Pathogenic Fungus Aspergillus Fumigatus, Gottfried Wilhelm
    Leibniz Universität Hannover, 2009.
date_created: 2018-12-11T12:03:07Z
date_published: 2009-08-13T00:00:00Z
date_updated: 2021-01-12T07:43:13Z
day: '13'
extern: 1
main_file_link:
- open_access: '0'
  url: http://edok01.tib.uni-hannover.de/edoks/e01dh09/609861891.pdf
month: '08'
page: 1 - 72
publication_status: published
publisher: Gottfried Wilhelm Leibniz Universität Hannover
publist_id: '3058'
quality_controlled: 0
status: public
title: Biosynthesis of Galactofuranose Containing Glycans and Their Relevance for
  the Pathogenic Fungus Aspergillus fumigatus
type: dissertation
year: '2009'
...
---
_id: '3291'
abstract:
- lang: eng
  text: 'The filamentous fungus Aspergillus fumigatus is responsible for a lethal
    disease called Invasive Aspergillosis that affects immunocompromised patients.
    This disease, like other human fungal diseases, is generally treated by compounds
    targeting the primary fungal cell membrane sterol. Recently, glucan synthesis
    inhibitors were added to the limited antifungal arsenal and encouraged the search
    for novel targets in cell wall biosynthesis. Although galactomannan is a major
    component of the A. fumigatus cell wall and extracellular matrix, the biosynthesis
    and role of galactomannan are currently unknown. By a targeted gene deletion approach,
    we demonstrate that UDP-galactopyranose mutase, a key enzyme of galactofuranose
    metabolism, controls the biosynthesis of galactomannan and galactofuranose containing
    glycoconjugates. The glfA deletion mutant generated in this study is devoid of
    galactofuranose and displays attenuated virulence in a low-dose mouse model of
    invasive aspergillosis that likely reflects the impaired growth of the mutant
    at mammalian body temperature. Furthermore, the absence of galactofuranose results
    in a thinner cell wall that correlates with an increased susceptibility to several
    antifungal agents. The UDP-galactopyranose mutase thus appears to be an appealing
    adjunct therapeutic target in combination with other drugs against A. fumigatus.
    Its absence from mammalian cells indeed offers a considerable advantage to achieve
    therapeutic selectivity. '
author:
- first_name: Philipp S
  full_name: Philipp Schmalhorst
  id: 309D50DA-F248-11E8-B48F-1D18A9856A87
  last_name: Schmalhorst
  orcid: 0000-0002-5795-0133
- first_name: Sven
  full_name: Krappmann, Sven
  last_name: Krappmann
- first_name: Wouter
  full_name: Vervecken, Wouter
  last_name: Vervecken
- first_name: Manfred
  full_name: Rohde, Manfred
  last_name: Rohde
- first_name: Meike
  full_name: Müller, Meike
  last_name: Müller
- first_name: Gerhard
  full_name: Braus, Gerhard H.
  last_name: Braus
- first_name: Roland
  full_name: Contreras, Roland
  last_name: Contreras
- first_name: Armin
  full_name: Braun, Armin
  last_name: Braun
- first_name: Hans
  full_name: Bakker, Hans
  last_name: Bakker
- first_name: Françoise
  full_name: Routier, Françoise H
  last_name: Routier
citation:
  ama: Schmalhorst PS, Krappmann S, Vervecken W, et al. Contribution of galactofuranose
    to the virulence of the opportunistic pathogen Aspergillus fumigatus. <i>Eukaryotic
    Cell</i>. 2008;7(8):1268-1277. doi:<a href="https://doi.org/10.1128/EC.00065-08">10.1128/EC.00065-08</a>
  apa: Schmalhorst, P. S., Krappmann, S., Vervecken, W., Rohde, M., Müller, M., Braus,
    G., … Routier, F. (2008). Contribution of galactofuranose to the virulence of
    the opportunistic pathogen Aspergillus fumigatus. <i>Eukaryotic Cell</i>. American
    Society for Microbiology. <a href="https://doi.org/10.1128/EC.00065-08">https://doi.org/10.1128/EC.00065-08</a>
  chicago: Schmalhorst, Philipp S, Sven Krappmann, Wouter Vervecken, Manfred Rohde,
    Meike Müller, Gerhard Braus, Roland Contreras, Armin Braun, Hans Bakker, and Françoise
    Routier. “Contribution of Galactofuranose to the Virulence of the Opportunistic
    Pathogen Aspergillus Fumigatus.” <i>Eukaryotic Cell</i>. American Society for
    Microbiology, 2008. <a href="https://doi.org/10.1128/EC.00065-08">https://doi.org/10.1128/EC.00065-08</a>.
  ieee: P. S. Schmalhorst <i>et al.</i>, “Contribution of galactofuranose to the virulence
    of the opportunistic pathogen Aspergillus fumigatus,” <i>Eukaryotic Cell</i>,
    vol. 7, no. 8. American Society for Microbiology, pp. 1268–1277, 2008.
  ista: Schmalhorst PS, Krappmann S, Vervecken W, Rohde M, Müller M, Braus G, Contreras
    R, Braun A, Bakker H, Routier F. 2008. Contribution of galactofuranose to the
    virulence of the opportunistic pathogen Aspergillus fumigatus. Eukaryotic Cell.
    7(8), 1268–1277.
  mla: Schmalhorst, Philipp S., et al. “Contribution of Galactofuranose to the Virulence
    of the Opportunistic Pathogen Aspergillus Fumigatus.” <i>Eukaryotic Cell</i>,
    vol. 7, no. 8, American Society for Microbiology, 2008, pp. 1268–77, doi:<a href="https://doi.org/10.1128/EC.00065-08">10.1128/EC.00065-08</a>.
  short: P.S. Schmalhorst, S. Krappmann, W. Vervecken, M. Rohde, M. Müller, G. Braus,
    R. Contreras, A. Braun, H. Bakker, F. Routier, Eukaryotic Cell 7 (2008) 1268–1277.
date_created: 2018-12-11T12:02:29Z
date_published: 2008-06-13T00:00:00Z
date_updated: 2021-01-12T07:42:26Z
day: '13'
doi: 10.1128/EC.00065-08
extern: 1
intvolume: '         7'
issue: '8'
month: '06'
page: 1268 - 1277
publication: Eukaryotic Cell
publication_status: published
publisher: American Society for Microbiology
publist_id: '3354'
quality_controlled: 0
status: public
title: Contribution of galactofuranose to the virulence of the opportunistic pathogen
  Aspergillus fumigatus
type: journal_article
volume: 7
year: '2008'
...