Medizinische Mikrobiologie & Krankenhaushygiene


Arbeitsgruppe Prof. Dr. med. Sören Schubert

Die Arbeitsgruppe von Sören Schubert untersucht Mechanismen und Pathogenitätsfaktoren, die extraintestinal pathogenen Escherichia coli (ExPEC) zu wichtigen Krankheitserregern in der Human- und Veterinärmedizin machen. Neben Harnwegsinfektionen und Wundinfektionen werden Sepsis und Neugeborenen-Meningitis durch ExPEC verursacht. Unser spezielles Augenmerk richtet sich auf die Charakterisierung von ExPEC Virulenzgenen, die ExPEC von kommensalen E. coli unterscheiden. In diesem Zusammenhang untersuchen wir sog. Pathogenitätsinseln von ExPEC, die über horizontalen Transfer teilweise über Gattungsgrenzen hinweg übertragen werden können und ein große Anzahl von Virulenzgenen tragen können. Vor allem die sog. High-Pathogenicity Island (HPI) von ExPEC ist Fokus unserer Arbeiten. Weitere Projekte betreffen den Bereich der klinischen Mikrobiologie und sind der Implementation neuer molekularer Testsysteme (MALDI-TOF MS, Multiplex real-time PCR) gewidmet, sowie der Entwicklung und Evaluation schneller Antibiotika-Resistenztestsystem.

Zur Arbeitsgruppe

Leitung

Prof. Sören Schubert, MD

Sören Schubert is adjunct professor of Medical Microbiology and Hospital Epidemiology at the Max von Pettenkofer-Institute of the Ludwig Maximilian University (LMU) in Munich, Germany. Sören Schubert studied medicine in Hamburg. He performed his thesis in the lab of Jürgen Heesemann at the University of Würzburg. In 1997 he moved to the Max von Pettenkofer-Institute at the LMU in Munich to establish an own research group. In 1999 he became a board-certified specialist physician in microbiology, virology and infection epidemiology. He received the young scientist award of the German Society for Hygiene and Microbiology (DGHM) in 2004 and completed his habilitation in 2007. Since then he is head of the microbiology diagnostic laboratories at the Max von Pettenkofer-institute and leader of his research group at the campus Großhadern.

AG Mitglieder

Sören Schubert, MD, Professor
Medical Microbiology and Hospital Epidemiology
E-Mail: sschubert@lmu.de

Birgit Groß, technician
E-Mail gross@mvp.lmu.de
Phone: +49 89 2180-78212

Forschung

Horizontal Transfer and Evolution of the High-Pathogenicity Island (HPI)

The fyuAirp gene cluster is definitely associated with virulence expression in highly pathogenic Yersinia species (Yersinia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica 1B). This 35-kb chromosomal DNA region meets all criteria of a pathogenicity island and it encodes for an iron uptake system mediated by the siderophore yersiniabactin.

Using PCR and southern hybridization techniques we could demonstrate that this Yersinia High-Pathogenicity Island (HPI) is distributed among extraintestinal pathogenic E. coli strains (ExPEC), predominantly in E. coli isolates from blood cultures and urine sample. By means of a bioassay we were able to detect the siderophore yersiniabactin in culture supernatants of HPI-positive isolates of E. coli and other Enterobacterales grown under iron starvation. This indicates the functional conservation of the Yersinia-HPI in those strains and raises questions about the reason for this iron uptake system in presence of other high-affinity iron uptake systems (e.g. enterochelin). We could further demonstrate that the HPI contributes to virulence in ExPEC and shows the highest association with virulence in extraintestinal pathogenic E. coli. Ongoing studies are directed towards the exact mechanisms of HPI in the virulence process.

Diversification of bacterial species and pathotypes is largely due to horizontal transferof diverse DNA elements such as plasmids, phages and genomic islands (e.g. pathogenicity islands, PAIs). A PAI called high-pathogenicity island (HPI) carrying genes involved in siderophore-mediated iron acquisition (yersiniabactin system) has previously been identified in and Y. enterocolitica IB strains, and has been characterized as an essential virulence factor in these species. Strikingly, an orthologous HPI is a widely distributed virulence determinant among Escherichia coli and other Enterobacterales which cause extraintestinal infections. The HPI of E. coli strain ECOR31 is distinct from all other HPIs described to date since the ECOR31 HPI comprises an additional 35-kb fragment at the right border compared to the HPI of other E. coli and Yersinia species. This part encodes for both a functional mating pair formation system and a DNA-processing region related to plasmid CloDF13 of Enterobacter cloacae. Upon induction of the P4-like integrase, the entire HPI of ECOR31 is precisely excised and circularized. The HPI of ECOR31 resembles integrative and conjugative elements termed ICE. It may represent the progenitor of the HPI found in Y. pestis and E. coli, revealing a missing link in the horizontal transfer of an element that contributes to microbial pathogenicity upon acquisition.

Host response to infections caused by extraintestinal pathogenic E. coli (ExPEC)

ExPEC infections of the urinary tract start with colonization of the bladder. It is known for several decades that adhesion molecules (e.g. type I fimbriae and P fimbriae) are involved in the attachment of ExPECs to urothelial cells. Recently, it has been shown that ExPEC exhibit an invasive phenotype, which leads to intracellular bacterial colonies (IBCs, “intracellular bacterial communities”). One project is dedicated to the characterization of ExPEC factors, which are involved in the invasive phenotype leading to formation of IBCs.

A second project regards ExPEC factors, which are produced during infection and subvert the innate immune response of the host. Previous studies of others have shown that ExPECs are able to modify or inhibit Toll-like receptor (TLR) mediated signaling pathways resulting in a decrease production of pro-inflammatory cytokines by host cells. Together with the group of Thomas Miethke (University of Mannheim) we could identify an ExPEC protein, which mimics the cytoplasmic TIR domain of TLRs leading to an inhibition of the MyD88 dependent signaling pathways of host cells.

Clinical Microbiology

The clinical microbiology projects are directed towards the establishing of novel diagnostic methods, mostly based on molecular techniques (e.g. diverse real-time PCRs). Part of the work is dedicated to the molecular typing of clinical relevant bacterial isolates from patients’ samples in order to unravel nosocomial transmission (patient to patient transmissions) of infective agents.

A further project deals with the use of MALDI-TOF techniques (Matrix Assisted Laser Desorption/Ionisation – Time of Flight) analyses for rapid differentiation of bacterial and fungi isolates as well as rapid antimicrobial susceptibility testing.

Publikationen

Top 10 Publikationen

Wang B, Briegel J, Krueger WA, Draenert R, Jung J, Weber A, Bogner J, Schubert S, Liebchen U, Frank S, Zoller M, Irlbeck M, Ney L, Weig T, Hinske L, Niedermayer S, Kilger E, Mohnle P, Grabein B. 2022. Ecological effects of selective oral decontamination on multidrug-resistance bacteria acquired in the intensive care unit: a case-control study over 5 years. Intensive Care Med 48:1165-1175.
Rehm N, Wallenstein A, Keizers M, Homburg S, Magistro G, Chagneau CV, Klimek H, Revelles O, Helloin E, Putze J, Nougayrede JP, Schubert S, Oswald E, Dobrindt U. 2022. Two Polyketides Intertwined in Complex Regulation: Posttranscriptional CsrA-Mediated Control of Colibactin and Yersiniabactin Synthesis in Escherichia coli. mBio 13:e0381421.
Pilatz A, Veeratterapillay R, Dimitropoulos K, Omar MI, Pradere B, Yuan Y, Cai T, Mezei T, Devlies W, Bruyere F, Bartoletti R, Koves B, Geerlings S, Schubert S, Grummet J, Mottet N, Wagenlehner F, Bonkat G. 2021. European Association of Urology Position Paper on the Prevention of Infectious Complications Following Prostate Biopsy. Eur Urol 79:11-15.
Schubert SP, R.; Gatermann, S.; Fünfstück, R.; Naber, K.G.; Schimanski, S.; Wagenlehner, F. 2020. Mikrobiologisch-infektiologische Qualitätsstandards (MiQ) - Teil 2, Harnwegsinfektionen, 3. ed, vol 02. Elsevier, Munich, Germany.
Pilatz A, Veeratterapillay R, Dimitropoulos K, Omar MI, Pradere B, Yuan Y, Cai T, Mezei T, Devlies W, Bruyere F, Bartoletti R, Koves B, Geerlings S, Schubert S, Grummet J, Mottet N, Wagenlehner F, Bonkat G. 2020. European Association of Urology Position Paper on the Prevention of Infectious Complications Following Prostate Biopsy. Eur Urol doi:10.1016/j.eururo.2020.10.019.
Schubert S, Kostrzewa M. 2017. MALDI-TOF MS in the Microbiology Laboratory: Current Trends. Curr Issues Mol Biol 23:17-20.
Jung JS, Hamacher C, Gross B, Sparbier K, Lange C, Kostrzewa M, Schubert S. 2016. Evaluation of a Semiquantitative Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Method for Rapid Antimicrobial Susceptibility Testing of Positive Blood Cultures. J Clin Microbiol 54:2820-2824.
Magistro G, Magistro C, Stief CG, Schubert S. 2018. A simple and highly efficient method for gene silencing in Escherichia coli. J Microbiol Methods 154:25-32.
Galardini M, Clermont O, Baron A, Busby B, Dion S, Schubert S, Beltrao P, Denamur E. 2020. Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study. PLoS Genet 16:e1009065.
Cirl C, Wieser A, Yadav M, Duerr S, Schubert S, Fischer H, Stappert D, Wantia N, Rodriguez N, Wagner H, Svanborg C, Miethke T. 2008. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat Med 14:399-406.

Auszeichnungen

Prof. Sören Schubert, MD

  • 1995 MD Award of the Julius-Maximilians-Universität, Würzburg
  • 2004 Young Scientist Award from the German Society for Hygiene and Microbiology (DGHM)