Biology subjects

Ruckdeschel, K.

Publications and source records attributed to Ruckdeschel, K..

4 recordsLinked to original sources

bioRxiv2026

Genes controlling polysaccharide synthesis, protein folding and basic metabolism ensure intra-host cell adaptation and replication of Yersinia enterocolitica

Pathogenesis of yersiniosis comprises cell-invasive events in which the bacteria subvert the endocytic-autophagolysosomal pathway of infected host cells to create an intracellular niche for bacterial replication. To determine potential virulence factors that enable intracellular proliferation of Yersinia enterocolitica, we performed a high-throughput transposon-directed insertion site sequencing approach (TraDIS) with infected epithelial HeLa cells. In this screen, we identified seven particular genes that have either metabolic activities in disulfide bond formation (dsbA), glutamine synthesis (glnA), and energy generation (acnB), or dictate synthesis of enterobacterial common antigen ECA (webB/C/F) and LPS (wzx). Individual knockout of the identified genes impaired intracellular replication of Yersinia. Furthermore, these mutants differentially affected host cell autophagy and the acidification of Yersinia-containing vacuoles (YCVs). The results indicate that glnA, acnB, dsbA, wecB, and wecC support autophagy-promoted, intracellular replication of Yersinia. Folding of yet to be defined proteins dependent on dsbA seems to be most critically required for mediating these events. A wzx-controlled LPS synthesis pathway appears implicated in preventing YCV acidification. These results suggest that autophagy induction and adjustment of Yersinia to the intravacuolar environment result from a multifactorial adaptation process that involves formation of a protective carbohydrate envelope and basic metabolic enzymes needed for the refinement of productive intracellular replication.

microbiology↗

bioRxiv2025

Immune activation of primary human macrophages is suppressed by the coordinated action of Yersinia effectors

In order to suppress the host immune response, numerous bacterial pathogens utilise a type 3 secretion system (T3SS) that injects effector proteins into host target cells. We investigated the T3SS effectors of Yersinia enterocolitica (Yops) for their individual and combined effects on gene expression, inflammasome formation and calcium signaling in primary human macrophages. YopP efficiently suppressed the up- and down-regulation of thousands of macrophage genes induced by the bacterias inflammatory stimuli. This was accompanied by parallel changes in histone 3-serine 10 phosphorylation, suggesting a higher-level regulatory mechanism. Surprisingly, YopM and YopQ counteracted selected YopP effects on gene expression, e.g., of cytokine pathways. A combination of YopP and YopQ, but not other combinations of Yops or any single Yop, reduced inflammasome formation. YopH alone blocked calcium transients in infected macrophages. We propose that the T3SS effectors of Yersinia antagonistically, synergistically or individually subdue major immune pathways of human macrophages to jointly suppress macrophage activation.

cell biology↗

bioRxiv2023

A Yersinia effector activates JAK-STAT signaling in human macrophages

The multifunctional Yersinia effector YopM inhibits effector triggered immunity and increases production of the anti-inflammatory cytokine Interleukin-10 (IL-10) to suppress the host immune response. Previously it was shown that YopM induces IL-10 gene expression by elevating phosphorylation of the serine-threonine kinase RSK1 in the nucleus of human macrophages. Using transcriptomics, we now show that YopM affects expression of genes encoding components of the JAK-STAT signaling pathway. Further analysis revealed that YopM mediates nuclear translocation of the transcription factor Stat3 in Y. enterocolitica infected macrophages and that knockdown of Stat3 inhibited YopM-induced IL-10 gene expression. YopM-induced Stat3 translocation did not depend on autocrine IL-10, activation of RSK1 or tyrosine phosphorylation of Stat3. Thus, besides activation of RSK1, stimulation of nuclear translocation of Stat3 is another mechanism by which YopM increases IL-10 gene expression in macrophages.

cell biology↗

bioRxiv2021

Epigenetic reprogramming of human macrophages by an intestinal pathogen

Various pathogens systematically reprogram gene expression in macrophages, but the underlying mechanisms are largely unknown. We investigated whether the enteropathogen Yersinia enterocolitica alters chromatin states to reprogram gene expression in primary human macrophages. Genome-wide chromatin immunoprecipitation (ChIP) seq analyses showed that pathogen-associated molecular patterns (PAMPs) induced up- or down-regulation of histone modifications (HMod) at approximately 14500 loci in promoters and enhancers. Effectors of Y. enterocolitica reorganized about half of these dynamic HMod, with the effector YopP being responsible for about half of these modulatory activities. The reorganized HMod were associated with genes involved in immune response and metabolism. Remarkably, the altered HMod also associated with 61 % of all 534 known Rho GTPase pathway genes, revealing a new level in Rho GTPase regulation and a new aspect of bacterial pathogenicity. Changes in HMod were associated to varying degrees with corresponding gene expression, e. g. depending on chromatin localization and cooperation of the HMod. In summary, infection with Y. enterocolitica remodels HMod in human macrophages to modulate key gene expression programs of the innate immune response. Author SummaryHuman pathogenic bacteria can affect epigenetic histone modifications to modulate gene expression in host cells. However, a systems biology analysis of this bacterial virulence mechanism in immune cells has not been performed. Here we analyzed genome-wide epigenetic histone modifications and associated gene expression changes in primary human macrophages infected with enteropathogenic Yersinia enterocolitica. We demonstrate that Yersinia virulence factors extensively modulate histone modifications and associated gene expression triggered by the pathogen-associated molecular patterns (PAMPs) of the bacteria. The epigenetically modulated genes are involved in several key pathways of the macrophage immune response, including the Rho GTPase pathway, revealing a novel level of Rho GTPase regulation by a bacterial pathogen. Overall, our findings provide an in-depth view of epigenetic and gene expression changes during host-pathogen interaction and might have further implications for understanding of the innate immune memory in macrophages.

microbiology↗