Biology subjects

Kazmaier, U.

Publications and source records attributed to Kazmaier, U..

2 recordsLinked to original sources

bioRxiv2025

Identification of pseudotetraivprolide from Pseudomonas entomophila give novel insights into the biosynthesis of detoxin/rimosamide-like anti-antibiotics

Novel variants of known natural product (NP) classes might guide our understanding of biosynthesis, mode of action and potential application as drugs for all members of such NP classes. Here we describe a novel member of the widespread detoxine/rimosamide-like (DRL) natural products named pseudotetraivprolide from Pseudomonas strains, which has the characteristic DRL-activity of protecting Bacillus cereus against the antibiotic blasticidin S. The generation of several deletion and complemented mutants, heterologous expression experiments, identification and structure elucidation of several derivatives, chemical synthesis of main derivatives, enzymatic characterization of individual biochemical steps and detailed homology modelling of enzyme complexes were performed. This allowed us to show the primary metabolism-derived malonyl CoA-ACP transacylase (AT) FabD acting as trans-AT in the biosynthesis, suggest an order for all late-stage modifications and provide a function for the three conserved hypothetical proteins PipDFG acting as last-step acetylation complex thereby stabilizing the final product.

microbiology↗

bioRxiv2024

Multiple clustered centrosomes in antigen-presenting cells foster T cell activation without MTOC polarization

Cellular polarization plays a pivotal role in regulating immunological processes and is often associated with centrosome reorientation. During immune synapse (IS) formation centrosome repositioning in lymphocytes assists in T cell activation. While a single centrosome, consisting of two centrioles, is present in T cells, antigen-presenting cells (APCs) such as dendritic cells (DCs) amplify centrioles during maturation leading to increased centrosome numbers upon immune activation. How centrosome amplification in DCs affects IS formation and T cell activation is unclear. In this study, we combine experimental data with mathematical and computational modelling to provide evidence that centrosome amplification in DCs enhances antigen-specific T cell activation. Extra centrioles in DCs form active centrosomes, which cluster during DC-T cell interactions and unlike in T cells, localize close to the cell center. Perturbing either centriole numbers or centrosome configuration in DCs results in impaired T cell activation. Collectively, our results highlight a crucial role for centrosome amplification and optimal centrosome positioning in APCs for controlling T cell responses.

cell biology↗