PD Dr. Christian Riedel

General Research Interests

Our group is interested in the adaptation of commensal and pathogenic bacteria of the (human) gastrointestinal tract to various habitats and the interaction of these bacteria with the host. One focus of interest is the role of a peptide-based communication system in regulation of virulence and biofilm formation of Listeria monocytogenes. A second area of research performed in the group is the investigation of mechanisms that govern host colonization by bifidobacteria as well as their effects on the mucosal immune system. For both groups of organisms, we study interactions with different populations of primary human macrophages and the subsequent effects on the immune system.

Listeria monocytogenes

L. monocytogenes is a ubiquitous, Gram-positive soil bacterium and a frequent contaminant of processed food products. Moreover, L. monocytogenes is able to cause life-threatening infections in immuno-compromised persons and a model organism for intracellular pathogenesis. Healthy individuals infected with L. monocytogenes display only mild symptoms of gastroenteritis or remain totally asymptomatic and a normal immune system efficiently eliminates the infection. Its abilities to withstand and grow under a wide range of environmental conditions (temperature, pH, salt, etc.) and to form biofilms on different surfaces make L. monocytogenes a serious concern in the food processing industries.

In a wide range of Gram-positive bacteria, biofilm formation, virulence, and other traits are regulated by peptide-based communication systems such as the agr system of L. monocytogenes. Previous studies of our group have shown that the L. monocytogenes agr system impacts both on virulence and biofilm formation (Riedel et al., 2009). Depending on the culture conditions, the biofilm matrix of L. monocytogenes may contain extracellular DNA and can be dispersed by DNase-treatment (Zetzmann et al., 2015). In a recently published study, we were able to identify the native, agrD-encoded autoinducing peptide of L. monocytogenes as well as several synthetic, antagonistic peptides (Zetzmann et al., 2016). A list of target genes of the agr system was compiled by genome-wide transcriptional profiling (Riedel et al., 2009). Current projects aim at dissecting the regulatory mechanisms of agr peptide sensing of L. monocytogenes.

Figure 1: CLSM images of biofilms of L. monocytogenes EGD-e wildtype (WT), ΔagrD, or the genetically complemented strain ΔagrD::pIMK2agrD (Comp) grown in 10-fold diluted (0.1BHI or normal BHI at 25 °C or 37 °C under static conditions for 24 h. Live bacteria are stained with Syto® 60 (red) and dead bacteria and eDNA with TOTO®-1 (green). Pictures were acquired on a Zeiss LSM700 confocal laser scanning microscope with a 63x objective. Image courtesy of M. Zetzmann (University of Ulm), all rights reserved.

Recently, another field of interest has emerged from our studies on biofilm formation and peptide-based communication. The ERA-IB2 consortium „SafeFood“ aims at investigating the effect of high pressure processing on integrity and viability of L. monocytogenes. Within the consortium, we develop novel molecular tools that allow conditional silencing or deletion of genes that can be targeted to increase sensitivity of L. monocytogenes to high pressure processing.

We further investigate interactions between L. monocytogenes and different populations of primary human macrophages (Neu et al., 2014) with the goal to characterize the contribution of the populations to elimination or persistence of infection. Using NGS transcriptional profiling and siRNA knockdown, a number of human genes were identified that may play a role in phagocytosis of L. monocytogenes, induction of appropriate immune responses, as well as immune evasion.

Figure 2: Scanning electron microscopy of an ex vivo differentiated human macrophage taking up L. monocytogenes bacteria. Inset: zoom-in on the part of the image marked with a white box depicting one bacterium captured during the process of phagocytosis. Image courtesy of C. Neu (University of Ulm), all rights reserved.

Bifidobacteria

Bifidobacteria are anaerobic Gram-positives and one of the most abundant bacterial phyla in the lower intestinal tract of humans. Particularly high numbers are observed in breast-fed infants and various health-promoting properties of bifidobacteria are attributed to their presence in the gut. Based on these health-promoting properties, bifidobacteria are increasingly used as so-called probiotic supplements in pharmaceutical and dairy products. For some strains anti-inflammatory effects have been reported in vitro and in preclinical studies. Thus, one potential field of application is their use as alternative or supplementary treatment in inflammatory conditions of the gastrointestinal tract.

Previous studies of our group have identified strains of the bifidobacteria that show high adhesion to intestinal epithelial cells and display potent anti-inflammatory activity in vitro and in murine models of colitis (Preising et al. 2010; Philippe et al. 2011, Grimm et al. 2015). In order to unravel the molecular mechanisms of host colonization and anti-inflammatory activity, we sequences the genomes of several strains of bifidobacteria (Zhurina et al. 2011; Zhurina et al., 2013; Bottacini et al., 2014) and identified a number of candidate genes potentially involved in these properties (Westermann et al. 2013). Past and current projects aim at investigating the role of these candidates to adhesion, colonization and inhibition of inflammation (e.g. Gleinser et al., 2012; Wei et al., 2014; Grimm et al., 2015, Wei et al., 2015). A further aspect is the potential use of bifidobacteria as vectors to for delivery of therapeutic genes into solid tumors (Osswald et al., 2015a). The development of molecular tools required to perform these studies are another important activity of the group (Grimm et al., 2014, Osswald et al., 2015b). A very recent project is dedicated to investigate the interaction of bifidobacteria with different subpopulations of human macrophages and the contribution of this interaction to the observed anti-inflammatory properties of bifidobacteria.

Figure 3: Overlay of brightfield and fluorescence microscopy images of primary human macrophages containing different B. bifidum strains labeled by plasmid-based expression of different fluorescent proteins inside. Pictures were acquired on a Zeiss Axio Observer.Z1 microscope with a 63x objective. Image courtesy of V. Grimm (University of Ulm), all rights reserved.

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