Dr. Lars Dietrich erforscht derzeit die Physiologie und das Verhalten von Bakterienbiofilmen, insbesondere wie Pseudomonas aeruginosa und andere Pathogene ihre Struktur, ihren Stoffwechsel und ihre Virulenz in Reaktion auf Umweltsignale (Licht, Sauerstoff, Immunmetabolite) regulieren. Seine Arbeiten nutzen quantitative Proteomik, Sensorik und Mikroskopie, um die räumlichen Gradienten und Mikroumgebungen innerhalb von Biofilmen zu kartieren und die molekularen Mechanismen der Pathogen-Persistenz zu entschlüsseln. Die Erkenntnisse sind relevant für die Entwicklung neuer Strategien gegen chronische Infektionen in der Medizin und für das Verständnis von Biofilm-Bildung in Wasser- und Abwassersystemen.
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Dr. Lars Dietrich
HU-FIS-Profil ↗Zeitraum: 10/2019 - 09/2020 Projektleitung: Dr. Lars Dietrich
Molecular Microbiology · 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 · DOI
Science · 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.