Dr. Lars Dietrich
Profil
Forschungsthemen1
Wie sozial-emotionale Fähigkeiten von Lehrkräften die sozial-emotionale Entwicklung von Schüler*innen beeinflussen.
Quelle ↗Zeitraum: 10/2019 - 09/2020 Projektleitung: Dr. Lars Dietrich
Mögliche Industrie-Partner10
Stand: 26.4.2026, 19:48:44 (Top-K=20, Min-Cosine=0.4)
- 53 Treffer59.4%
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- Engineering of New-Generation Protein Secretion Systems
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- Engineering of New-Generation Protein Secretion SystemsP59.4%
- Engineering of New-Generation Protein Secretion Systems
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- Engineering of New-Generation Protein Secretion SystemsP59.4%
- Engineering of New-Generation Protein Secretion Systems
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- Eukaryotic Unicellular Organism Biology – Systems Biology of the Control of Cell Growth and ProliferationP57.1%
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- Eukaryotic Unicellular Organism Biology – Systems Biology of the Control of Cell Growth and Proliferation
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- DYnamic control in hybrid plasmonic NAnopores: road to next generation multiplexed single MOlecule detection
- 12 Treffer55.9%
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- Systematic Models for Biological Systems Engineering Training Network
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- Systematic Models for Biological Systems Engineering Training Network
Protatuans-Etaireia Ereynas Viotechologias Monoprosopi Etaireia Periorisments Eythinis
P12 Treffer55.9%- Systematic Models for Biological Systems Engineering Training NetworkP55.9%
- Systematic Models for Biological Systems Engineering Training Network
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- Systematic Models for Biological Systems Engineering Training NetworkP55.9%
- Systematic Models for Biological Systems Engineering Training Network
- 40 Treffer55.9%
- EU: Simulation in Multiscale Physical and Biological Systems (STIMULATE)P55.9%
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Publikationen25
Top 25 nach Zitationen — Quelle: OpenAlex (BAAI/bge-m3 embedded für Matching).
Molecular Microbiology · 719 Zitationen · DOI
Certain members of the fluorescent pseudomonads produce and secrete phenazines. These heterocyclic, redox-active compounds are toxic to competing organisms, and the cause of these antibiotic effects has been the focus of intense research efforts. It is largely unknown, however, how pseudomonads themselves respond to - and survive in the presence of - these compounds. Using Pseudomonas aeruginosa DNA microarrays and quantitative RT-PCR, we demonstrate that the phenazine pyocyanin elicits the upregulation of genes/operons that function in transport [such as the resistance-nodulation-cell division (RND) efflux pump MexGHI-OpmD] and possibly in redox control (such as PA2274, a putative flavin-dependant monooxygenase), and downregulates genes involved in ferric iron acquisition. Strikingly, mexGHI-opmD and PA2274 were previously shown to be regulated by the PA14 quorum sensing network that controls the production of virulence factors (including phenazines). Through mutational analysis, we show that pyocyanin is the physiological signal for the upregulation of these quorum sensing-controlled genes during stationary phase and that the response is mediated by the transcription factor SoxR. Our results implicate phenazines as signalling molecules in both P. aeruginosa PA14 and PAO1.
Nature Chemical Biology · 584 Zitationen · DOI
Science · 447 Zitationen · DOI
It is thought that bacteria excrete redox-active pigments as antibiotics to inhibit competitors. In Pseudomonas aeruginosa, the endogenous antibiotic pyocyanin activates SoxR, a transcription factor conserved in Proteo- and Actinobacteria. In Escherichia coli, SoxR regulates the superoxide stress response. Bioinformatic analysis coupled with gene expression studies in P. aeruginosa and Streptomyces coelicolor revealed that the majority of SoxR regulons in bacteria lack the genes required for stress responses, despite the fact that many of these organisms still produce redox-active small molecules, which indicates that redox-active pigments play a role independent of oxidative stress. These compounds had profound effects on the structural organization of colony biofilms in both P. aeruginosa and S. coelicolor, which shows that "secondary metabolites" play important conserved roles in gene expression and development.
Journal of Bacteriology · 316 Zitationen · DOI
Many microbial species form multicellular structures comprising elaborate wrinkles and concentric rings, yet the rules governing their architecture are poorly understood. The opportunistic pathogen Pseudomonas aeruginosa produces phenazines, small molecules that act as alternate electron acceptors to oxygen and nitrate to oxidize the intracellular redox state and that influence biofilm morphogenesis. Here, we show that the depth occupied by cells within colony biofilms correlates well with electron acceptor availability. Perturbations in the environmental provision, endogenous production, and utilization of electron acceptors affect colony development in a manner consistent with redox control. Intracellular NADH levels peak before the induction of colony wrinkling. These results suggest that redox imbalance is a major factor driving the morphogenesis of P. aeruginosa biofilms and that wrinkling itself is an adaptation that maximizes oxygen accessibility and thereby supports metabolic homeostasis. This type of redox-driven morphological change is reminiscent of developmental processes that occur in metazoans.
Journal of Bacteriology · 311 Zitationen · DOI
The opportunistic pathogen Pseudomonas aeruginosa produces colorful, redox-active antibiotics called phenazines. Excretion of pyocyanin, the best-studied natural phenazine, is responsible for the bluish tint of sputum and pus associated with P. aeruginosa infections in humans. Although the toxicity of pyocyanin for other bacteria, as well as its role in eukaryotic infection, has been studied extensively, the physiological relevance of pyocyanin metabolism for the producing organism is not well understood. Pyocyanin reduction by P. aeruginosa PA14 is readily observed in standing liquid cultures that have consumed all of the oxygen in the medium. We investigated the physiological consequences of pyocyanin reduction by assaying intracellular concentrations of NADH and NAD+ in the wild-type strain and a mutant defective in phenazine production. We found that the mutant accumulated more NADH in stationary phase than the wild type. This increased accumulation correlated with a decrease in oxygen availability and was relieved by the addition of nitrate. Pyocyanin addition to a phenazine-null mutant also decreased intracellular NADH levels, suggesting that pyocyanin reduction facilitates redox balancing in the absence of other electron acceptors. Analysis of extracellular organic acids revealed that pyocyanin stimulated stationary-phase pyruvate excretion in P. aeruginosa PA14, indicating that pyocyanin may also influence the intracellular redox state by decreasing carbon flux through central metabolic pathways.
Nature Communications · 265 Zitationen · DOI
Antibiotic efficacy can be antagonized by bioactive metabolites and other drugs present at infection sites. Pseudomonas aeruginosa, a common cause of biofilm-based infections, releases metabolites called phenazines that accept electrons to support cellular redox balancing. Here, we find that phenazines promote tolerance to clinically relevant antibiotics, such as ciprofloxacin, in P. aeruginosa biofilms and that this effect depends on the carbon source provided for growth. We couple stable isotope labeling with stimulated Raman scattering microscopy to visualize biofilm metabolic activity in situ. This approach shows that phenazines promote metabolism in microaerobic biofilm regions and influence metabolic responses to ciprofloxacin treatment. Consistent with roles of specific respiratory complexes in supporting phenazine utilization in biofilms, phenazine-dependent survival on ciprofloxacin is diminished in mutants lacking these enzymes. Our work introduces a technique for the chemical imaging of biosynthetic activity in biofilms and highlights complex interactions between bacterial products, their effects on biofilm metabolism, and the antibiotics we use to treat infections.
Nature Reviews Microbiology · 262 Zitationen · DOI
Control of Candida albicans Metabolism and Biofilm Formation by Pseudomonas aeruginosa Phenazines
2013mBio · 244 Zitationen · DOI
Candida albicans has developmental programs that govern transitions between yeast and filamentous morphologies and between unattached and biofilm lifestyles. Here, we report that filamentation, intercellular adherence, and biofilm development were inhibited during interactions between Candida albicans and Pseudomonas aeruginosa through the action of P. aeruginosa-produced phenazines. While phenazines are toxic to C. albicans at millimolar concentrations, we found that lower concentrations of any of three different phenazines (pyocyanin, phenazine methosulfate, and phenazine-1-carboxylate) allowed growth but affected the development of C. albicans wrinkled colony biofilms and inhibited the fungal yeast-to-filament transition. Phenazines impaired C. albicans growth on nonfermentable carbon sources and led to increased production of fermentation products (ethanol, glycerol, and acetate) in glucose-containing medium, leading us to propose that phenazines specifically inhibited respiration. Methylene blue, another inhibitor of respiration, also prevented the formation of structured colony biofilms. The inhibition of filamentation and colony wrinkling was not solely due to lowered extracellular pH induced by fermentation. Compared to smooth, unstructured colonies, wrinkled colony biofilms had higher oxygen concentrations within the colony, and wrinkled regions of these colonies had higher levels of respiration. Together, our data suggest that the structure of the fungal biofilm promotes access to oxygen and enhances respiratory metabolism and that the perturbation of respiration by bacterial molecules such as phenazines or compounds with similar activities disrupts these pathways. These findings may suggest new ways to limit fungal biofilms in the context of disease. IMPORTANCE Many of the infections caused by Candida albicans, a major human opportunistic fungal pathogen, involve both morphological transitions and the formation of surface-associated biofilms. Through the study of C. albicans interactions with the bacterium Pseudomonas aeruginosa, which often coinfects with C. albicans, we have found that P. aeruginosa-produced phenazines modulate C. albicans metabolism and, through these metabolic effects, impact cellular morphology, cell-cell interactions, and biofilm formation. We suggest that the structure of C. albicans biofilms promotes access to oxygen and enhances respiratory metabolism and that the perturbation of respiration by phenazines inhibits biofilm development. Our findings not only provide insight into interactions between these species but also provide valuable insights into novel pathways that could lead to the development of new therapies to treat C. albicans infections.
Convergent Evolution of Hyperswarming Leads to Impaired Biofilm Formation in Pathogenic Bacteria
2013Cell Reports · 175 Zitationen · DOI
Most bacteria in nature live in surface-associated communities rather than planktonic populations. Nonetheless, how surface-associated environments shape bacterial evolutionary adaptation remains poorly understood. Here, we show that subjecting Pseudomonas aeruginosa to repeated rounds of swarming, a collective form of surface migration, drives remarkable parallel evolution toward a hyperswarmer phenotype. In all independently evolved hyperswarmers, the reproducible hyperswarming phenotype is caused by parallel point mutations in a flagellar synthesis regulator, FleN, which locks the naturally monoflagellated bacteria in a multiflagellated state and confers a growth rate-independent advantage in swarming. Although hyperswarmers outcompete the ancestral strain in swarming competitions, they are strongly outcompeted in biofilm formation, which is an essential trait for P. aeruginosa in environmental and clinical settings. The finding that evolution in swarming colonies reliably produces evolution of poor biofilm formers supports the existence of an evolutionary trade-off between motility and biofilm formation.
PLoS Pathogens · 174 Zitationen · DOI
In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF) and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic-di-GMP (c-di-GMP), and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol stimulation of c-di-GMP. Multiple lines of evidence indicate that ethanol stimulates WspR signaling through its cognate sensor WspA, and promotes WspR-dependent activation of Pel exopolysaccharide production, which contributes to biofilm maturation. We also found that ethanol stimulation of WspR promoted P. aeruginosa colonization of CF airway epithelial cells. P. aeruginosa production of phenazines occurs both in the CF lung and in culture, and phenazines enhance ethanol production by C. albicans. Using a C. albicans adh1/adh1 mutant with decreased ethanol production, we found that fungal ethanol strongly altered the spectrum of P. aeruginosa phenazines in favor of those that are most effective against fungi. Thus, a feedback cycle comprised of ethanol and phenazines drives this polymicrobial interaction, and these relationships may provide insight into why co-infection with both P. aeruginosa and C. albicans has been associated with worse outcomes in cystic fibrosis.
Proceedings of the National Academy of Sciences · 172 Zitationen · DOI
Evolutionary biologists have postulated that several fitness advantages may be conferred by the maintenance of duplicate genes, including environmental adaptation resulting from differential regulation. We examined the expression and physiological contributions of two redundant operons in the adaptable bacterium Pseudomonas aeruginosa PA14. These operons, phzA1-G1 (phz1) and phzA2-G2 (phz2), encode nearly identical sets of proteins that catalyze the synthesis of phenazine-1-carboxylic acid, the precursor for several phenazine derivatives. Phenazines perform diverse roles in P. aeruginosa physiology and act as virulence factors during opportunistic infections of plant and animal hosts. Although reports have indicated that phz1 is regulated by the Pseudomonas quinolone signal, factors controlling phz2 expression have not been identified, and the relative contributions of these redundant operons to phenazine biosynthesis have not been evaluated. We found that in liquid cultures, phz1 was expressed at higher levels than phz2, although phz2 showed a greater contribution to phenazine production. In colony biofilms, phz2 was expressed at high levels, whereas phz1 expression was not detectable, and phz2 was responsible for virtually all phenazine production. Analysis of mutants defective in quinolone signal synthesis revealed a critical role for 4-hydroxy-2-heptylquinoline in phz2 induction. Finally, deletion of phz2, but not of phz1, decreased lung colonization in a murine model of infection. These results suggest that differential regulation of the redundant phz operons allows P. aeruginosa to adapt to diverse environments.
Proceedings of the National Academy of Sciences · 168 Zitationen · DOI
Redox-cycling compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux pump MexGHI-OpmD in the opportunistic pathogen Pseudomonas aeruginosa Previous studies of P. aeruginosa virulence, physiology, and biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA). In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin is presumed to proceed through the intermediate 5-methylphenazine-1-carboxylate (5-Me-PCA), a reactive compound that has eluded detection in most laboratory samples. Here, we apply electrochemical methods to directly detect 5-Me-PCA and find that it is transported by MexGHI-OpmD in P. aeruginosa strain PA14 planktonic and biofilm cells. We also show that 5-Me-PCA is sufficient to fully induce MexGHI-OpmD expression and that it is required for wild-type colony biofilm morphogenesis. These physiological effects are consistent with the high redox potential of 5-Me-PCA, which distinguishes it from other well-studied P. aeruginosa phenazines. Our observations highlight the importance of this compound, which was previously overlooked due to the challenges associated with its detection, in the context of P. aeruginosa gene expression and multicellular behavior. This study constitutes a unique demonstration of efflux-based self-resistance, controlled by a simple circuit, in a Gram-negative pathogen.
Nature Communications · 167 Zitationen · DOI
Trends in Biochemical Sciences · 164 Zitationen · DOI
Research in Microbiology · 159 Zitationen · DOI
Physics in Medicine and Biology · 158 Zitationen · DOI
A new online imaging approach, linac-integrated cone beam CT (CBCT), has been developed over the past few years. It has the advantage that a patient can be examined in their treatment position directly before or during a radiotherapy treatment. Unfortunately, respiratory organ motion, one of the largest intrafractional organ motions, often leads to artefacts in the reconstructed 3D images. One way to take this into account is to register the breathing phase during image acquisition for a phase-correlated image reconstruction. Therefore, the main focus of this work is to present a system which has the potential to investigate the correlation between internal (movement of the diaphragm) and external (data of a respiratory gating system) information about breathing phase and amplitude using an inline CBCT scanner. This also includes a feasibility study about using the acquired information for a respiratory-correlated 4D CBCT reconstruction. First, a moving lung phantom was used to develop and to specify the required methods which are based on an image reconstruction using only projections belonging to a certain moving phase. For that purpose, the corresponding phase has to be detected for each projection. In the case of the phantom, an electrical signal allows one to track the movement in real time. The number of projections available for the image reconstruction depends on the breathing phase and the size of the position range from which projections should be used for the reconstruction. The narrower this range is, the better the inner structures can be located, but also the noise of the images increases due to the limited number of projections. This correlation has also been analysed. In a second step, the methods were clinically applied using data sets of patients with lung tumours. In this case, the breathing phase was detected by an external gating system (AZ-733V, Anzai Medical Co.) based on a pressure sensor attached to the patient's abdominal region with a fixation belt. The comparison of the reconstructed 4D CBCT images and the corresponding 4D CT images used for the treatment planning provides the required information for the calculation of possible setup errors. So, a repositioning of the patient is feasible even though the patient moves due to respiration. In addition to the external signal, the position of the diaphragm in the cranial-caudal direction could be extracted from each projection. Both independent sources of information show a very good agreement of the phase and even the amplitude of the movement and the external signal respectively. This suggests the usability of such a system for a gated dose delivery approach. However, more studies involving patients with different incidences have to be carried out to confirm these first results.
Journal of Molecular Biology · 138 Zitationen · DOI
EMBO Reports · 134 Zitationen · DOI
eLife · 124 Zitationen · DOI
Hypoxia is a common challenge faced by bacteria during associations with hosts due in part to the formation of densely packed communities (biofilms). <i>cbb</i><sub>3</sub>-type cytochrome <i>c</i> oxidases, which catalyze the terminal step in respiration and have a high affinity for oxygen, have been linked to bacterial pathogenesis. The pseudomonads are unusual in that they often contain multiple full and partial (i.e. 'orphan') operons for <i>cbb</i><sub>3</sub>-type oxidases and oxidase subunits. Here, we describe a unique role for the orphan catalytic subunit CcoN4 in colony biofilm development and respiration in the opportunistic pathogen <i>Pseudomonas aeruginosa</i> PA14. We also show that CcoN4 contributes to the reduction of phenazines, antibiotics that support redox balancing for cells in biofilms, and to virulence in a <i>Caenorhabditis elegans</i> model of infection. These results highlight the relevance of the colony biofilm model to pathogenicity and underscore the potential of <i>cbb</i><sub>3</sub>-type oxidases as therapeutic targets.
Nature Communications · 121 Zitationen · DOI
Monitoring spatial distribution of metabolites in multicellular structures can enhance understanding of the biochemical processes and regulation involved in cellular community development. Here we report on an electrochemical camera chip capable of simultaneous spatial imaging of multiple redox-active phenazine metabolites produced by Pseudomonas aeruginosa PA14 colony biofilms. The chip features an 8 mm × 8 mm array of 1,824 electrodes multiplexed to 38 parallel output channels. Using this chip, we demonstrate potential-sweep-based electrochemical imaging of whole-biofilms at measurement rates in excess of 0.2 s per electrode. Analysis of mutants with various capacities for phenazine production reveals distribution of phenazine-1-carboxylic acid (PCA) throughout the colony, with 5-methylphenazine-1-carboxylic acid (5-MCA) and pyocyanin (PYO) localized to the colony edge. Anaerobic growth on nitrate confirms the O2-dependence of PYO production and indicates an effect of O2 availability on 5-MCA synthesis. This integrated-circuit-based technique promises wide applicability in detecting redox-active species from diverse biological samples.
Nature Methods · 119 Zitationen · DOI
Trends in Microbiology · 110 Zitationen · DOI
Radiation Oncology · 110 Zitationen · DOI
The cone beam CT attached to a LINAC allows the acquisition of a CT scan of the patient in treatment position directly before treatment. Its image quality is sufficient for determining target point correction vectors. With the presented workflow, a target point correction within a clinically reasonable time frame is possible. This increases the treatment precision, and potentially the complex patient fixation techniques will become dispensable.
Proceedings of the National Academy of Sciences · 100 Zitationen · DOI
Diverse organisms secrete redox-active antibiotics, which can be used as extracellular electron shuttles by resistant microbes. Shuttle-mediated metabolism can support survival when substrates are available not locally but rather at a distance. Such conditions arise in multicellular communities, where the formation of chemical gradients leads to resource limitation for cells at depth. In the pathogenic bacterium <i>Pseudomonas aeruginosa</i> PA14, antibiotics called phenazines act as oxidants to balance the intracellular redox state of cells in anoxic biofilm subzones. PA14 colony biofilms show a profound morphogenic response to phenazines resulting from electron acceptor-dependent inhibition of ECM production. This effect is reminiscent of the developmental responses of some eukaryotic systems to redox control, but for bacterial systems its mechanistic basis has not been well defined. Here, we identify the regulatory protein RmcA and show that it links redox conditions to PA14 colony morphogenesis by modulating levels of bis-(3',5')-cyclic-dimeric-guanosine (c-di-GMP), a second messenger that stimulates matrix production, in response to phenazine availability. RmcA contains four Per-Arnt-Sim (PAS) domains and domains with the potential to catalyze the synthesis and degradation of c-di-GMP. Our results suggest that phenazine production modulates RmcA activity such that the protein degrades c-di-GMP and thereby inhibits matrix production during oxidizing conditions. RmcA thus forms a mechanistic link between cellular redox sensing and community morphogenesis analogous to the functions performed by PAS-domain-containing regulatory proteins found in complex eukaryotes.
Phytopathology · 98 Zitationen · DOI
Pseudomonas CMR12a was previously selected as an efficient biocontrol strain producing phenazines and cyclic lipopeptides (CLPs). In this study, biocontrol capacity of Pseudomonas CMR12a against Rhizoctonia root rot of bean and the involvement of phenazines and CLPs in this ability were tested. Two different anastomosis groups (AGs) of Rhizoctonia solani, the intermediately aggressive AG 2-2 and the highly aggressive AG 4 HGI, were included in growth-chamber experiments with bean plants. The wild-type strain CMR12a dramatically reduced disease severity caused by both R. solani AGs. A CLP-deficient and a phenazine-deficient mutant of CMR12a still protected bean plants, albeit to a lesser extent compared with the wild type. Two mutants deficient in both phenazine and CLP production completely lost their biocontrol activity. Disease-suppressive capacity of CMR12a decreased after washing bacteria before application to soil and thereby removing metabolites produced during growth on plate. In addition, microscopic observations revealed pronounced branching of hyphal tips of both R. solani AGs in the presence of CMR12a. More branched and denser mycelium was also observed for the phenazine-deficient mutant; however, neither the CLP-deficient mutant nor the mutants deficient in both CLPs and phenazines influenced hyphal growth. Together, results demonstrate the involvement of phenazines and CLPs during Pseudomonas CMR12a-mediated biocontrol of Rhizoctonia root rot of bean.
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Identität, Organisation und Kontakt aus HU-FIS.
- Name
- Dr. Lars Dietrich
- Titel
- Dr.
- Fakultät
- Kultur-, Sozial- und Bildungswissenschaftliche Fakultät
- Institut
- Institut für Rehabilitationswissenschaften
- Arbeitsgruppe
- Pädagogik bei psychosozialen Beeinträchtigungen
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- +49 30 2093-66762
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- 26.4.2026, 01:03:57