Publications by authors named "Kristina Herold"

3 Publications

  • Page 1 of 1

The impact of episporic modification of on virulence and interaction with phagocytes.

Comput Struct Biotechnol J 2021 20;19:880-896. Epub 2021 Jan 20.

Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), Jena, Germany.

Fungal infections caused by the ancient lineage Mucorales are emerging and increasingly reported in humans. Comprehensive surveys on promising attributes from a multitude of possible virulence factors are limited and so far, focused on and . This study addresses a systematic approach to monitor phagocytosis after physical and enzymatic modification of the outer spore wall of , one of the major causative agents of mucormycosis. Episporic modifications were performed and their consequences on phagocytosis, intracellular survival and virulence by murine alveolar macrophages and in an invertebrate infection model were elucidated. While depletion of lipids did not affect the phagocytosis of both strains, delipidation led to attenuation of LCA strain but appears to be dispensable for infection with LCV strain in the settings used in this study. Combined glucano-proteolytic treatment was necessary to achieve a significant decrease of virulence of the LCV strain in during maintenance of the full potential for spore germination as shown by a novel automated germination assay. Proteolytic and glucanolytic treatments largely increased phagocytosis compared to alive resting and swollen spores. Whilst resting spores barely (1-2%) fuse to lysosomes after invagination in to phagosomes, spore trypsinization led to a 10-fold increase of phagolysosomal fusion as measured by intracellular acidification. This is the first report of a polyphasic measurement of the consequences of episporic modification of a mucormycotic pathogen in spore germination, spore surface ultrastructure, phagocytosis, stimulation of Toll-like receptors (TLRs), phagolysosomal fusion and intracellular acidification, apoptosis, generation of reactive oxygen species (ROS) and virulence.
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http://dx.doi.org/10.1016/j.csbj.2021.01.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851798PMC
January 2021

Inflammation-Dysregulated inflammatory response and strategies for treatment.

Acta Physiol (Oxf) 2019 07 16;226(3):e13284. Epub 2019 May 16.

Klinik für Innere Medizin III, AG Experimentelle Nephrologie, Universitätsklinikum Jena, Jena, Germany.

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http://dx.doi.org/10.1111/apha.13284DOI Listing
July 2019

Imidazopyridines as Potent KDM5 Demethylase Inhibitors Promoting Reprogramming Efficiency of Human iPSCs.

iScience 2019 Feb 11;12:168-181. Epub 2019 Jan 11.

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, ImNeuenheimer Feld 364, 69120 Heidelberg, Germany. Electronic address:

Pioneering human induced pluripotent stem cell (iPSC)-based pre-clinical studies have raised safety concerns and pinpointed the need for safer and more efficient approaches to generate and maintain patient-specific iPSCs. One approach is searching for compounds that influence pluripotent stem cell reprogramming using functional screens of known drugs. Our high-throughput screening of drug-like hits showed that imidazopyridines-analogs of zolpidem, a sedative-hypnotic drug-are able to improve reprogramming efficiency and facilitate reprogramming of resistant human primary fibroblasts. The lead compound (O4I3) showed a remarkable OCT4 induction, which at least in part is due to the inhibition of H3K4 demethylase (KDM5, also known as JARID1). Experiments demonstrated that KDM5A, but not its homolog KDM5B, serves as a reprogramming barrier by interfering with the enrichment of H3K4Me3 at the OCT4 promoter. Thus our results introduce a new class of KDM5 chemical inhibitors and provide further insight into the pluripotency-related properties of KDM5 family members.
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http://dx.doi.org/10.1016/j.isci.2019.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354736PMC
February 2019
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