Cellular Microbiology
Main Emphasis
Tuberculosis (TB) is the most important human bacterial infection of humans worldwide topping the pathogen list with antimicrobial resistances. Its agent, Mycobacterium tuberculosis, is a facultative intracellular pathogen able to survive and proliferate inside host phagocytes such as macrophages and neutrophils. In the context of pulmonary infections, we also study microbiota functions and resilience, as well as the pathobiology of the emerging pathobiont, Stenotrophomonas maltophilia, in mixed fungal and bacterial biofilms. We hypothesize, that a pathogen's host niche determines its fate, transmission, innate and acquired immune responses and pathogenesis as well as post infection disease, and ultimately, anti-bacterial drug efficacy. Therefore, we study host-pathogen interactions in lung infections, in order to improve prophylaxis, to develop novel treatments including nanomedicines and biomarker-informed host-directed therapies, and to prevent long-term disease.
Hypothesis:
A pathogen's host niche determines survival, immune defense, pathogenesis, transmission and treatment success.
Mission:
Host-pathogen interaction studies of lung infections to improve prophylaxis, biomarker lead therapy and long-term disease
Infections:
M. tuberculosis (Mtb), S. maltophilia (Sm), K. pneumoniae, IAV, CoV
Objectives:
I) New biomarkers for therapeutic success, disease status and long-term outcome;
II) new drugs, nanomedicines, phage, plasma and host-directed therapy of TB and other AMR infections;
III) microbiome function and resilience upon infection and treatment;
IV) biofilm pathobiology and AMR evolution
- Leibniz Research Alliance INFECTIONS
InfUrb (Speaker): Spread of antimicrobial resistance, -2025 - Leibniz Research Campus EvoLung
Interaction between microbiota, host and tuberculosis,-2024 - German Center for Infection Research (DZIF) (BMBF)
TTU-TB, Neutrophil signatures in tuberculosis, -2025 - TB Sequel II (BMBF Afrika)
Post tuberculosis disease, -2025 - FLAV4AMR (JIPAMR/BMBF)
Flavodoxin inhibitors to kill resistant bacteria, -2023 - VITALITY(EDCTP)
Vitamin D for AdoLescents with HIV to reduce musculoskeletal morbidity and ImmunopaThologY, -2025 - ERA4TB (Horizon 2020; IMI)
European Regimen Accelerator for Tuberculosis, -2025 - PlasmaPlusCorona (BMBF)
Cold plasma against SARS Cov2 and biofilm forming lung pathogens, -2024 - LPI- Basic Technology 1 (BT 1)
Multi-Dimensional, multimodal, intelligent Imaging Plattforms, tuberculosis in vivo models, -2025 - Regulatory functions of oxidative/antioxidative processes during host–pathogen interactions in tuberculosis
(DFG, East Mediterranean Cooperation), -2024
External Cooperations
- Alexander Apt, Vladimir Yeremeev, Central Institute for Tuberculosis, Moscow, Russia; Properties on susceptibility and resistance in tuberculosis
- John Baines, MPI for Evolutionary Biology, Plön: Pulmonary microbiota in infection and immunity
- Moran Benhar, Technion-Israel Institute of Technology, Haifa, Israel: Redox reactions in tuberculosis
- Lea Ann Dailey, University Vienna: Targeted nanocarrier for anti-TB drug delivery
- Claus Feldmann, KIT Karlsruhe: : Targeted nanocarrier for anti-TB drug delivery
- Ulrich Günther, University Lübeck: Metabolome of tuberculosis infected cells
- Bernhard Hube, HKI Jena: Mixed biofilms with albicans
- Paul M. Kelly, University of Lusaka, Zambia: Vitamin D in infection and immunity
- Katharina Kranzer, LSHTM, London/Harare: Vitamin D in infection and immunity
- Manfred Lutz, University of Würzburg: Myeloid derived suppressor cells in mycobacterial infections
- Esther Meyron-Holtz, Technion-Israel Institute of Technology, Haifa, Israel: Iron in tuberculosis
- Andrea Rachow, LMU Munich: Post Tuberculosis disease
- Frank Schmidt, Weill Cornell Medicine Qatar: Proteomics of host - pathogen interactions
- Albert Sickmann, ISAS, Dortmund: Proteomics of host - pathogen interactions
- Wolfgang Streit, University Hamburg: Stenotrophomonas maltophilia pathobiology
- Jayne Sutherland, LSHTM/The Gambia: Post Tuberculosis disease
- Thomas von Woedtke, INP, Greifswald: Cold plasma in anti-infection therapy
Infection Biology
- Safety lab to work with BSL3 microorganisms such as Mycobacterium tuberculosis
- Aerosol infection model for tuberculosis (BSL3)
- Vaccine and anti-microbial drug testing
- Microbiome analysis (16s RNA sequencing, metagenomics, FISH, bioinformatics)
- In vivo and in vitro imaging (under BSL3 conditions)
- In vitro Infection models in primary cells from mouse and human (BSL3)
- In vivo infection models for Klebsiella pneumonia infection
- Stenotrophomonas maltophilia and mixed biofilm studies between bacteria and yeasts
- Air-liquid interface lung epithelial cell model for biofilm studies
- Bacteriophage collection
Infection Immunology
- FACS (BSL2 and 3)
- Histology Immunohistology
- Cytokine- and chemokine assays
- T-cell-Assays
- Quantitative Real-time PCR
- RNAseq
Cellular microbiology
- Intracellular trafficking studies of pathogens in host cells, confocal microscopy
- Live cell microscopy (BSL2 and 3)
- Primary cell cultures: human, mouse; macrophages, neutrophils, dendritic cells, lymphocytes, lung epithelial cells
- Subcellular fractionation, phagosome isolation
- Cell death assays
- siRNA-based knock-down
- Reporter strain of tuberculosis and S. maltophilia
Biochemistry
- SDS-PAGE, western blot
- Liposome technology
- Glycolipid isolation
- Thin layer chromatography
2024
Blankson, HNA, Kamara, RF, Barilar, I, Andres, S, Conteh, OS, Dallenga, T, Foray, L, Maurer, F, Kranzer, K & Utpatel, C et al. 2024, 'Molecular determinants of multidrug-resistant tuberculosis in Sierra Leone', Microbiology spectrum, Jg. 12, Nr. 3, S. e0240523. https://doi.org/10.1128/spectrum.02405-23
Coves, X, Mamat, U, Conchillo-Solé, O, Huedo, P, Bravo, M, Gómez, A-C, Krohn, I, Streit, WR, Schaible, UE & Gibert, I et al. 2024, 'The Mla system and its role in maintaining outer membrane barrier function in Stenotrophomonas maltophilia', Frontiers in Cellular and Infection Microbiology, Jg. 14, S. 1346565. https://doi.org/10.3389/fcimb.2024.1346565
Galano-Frutos, JJ, Maity, R, Iguarbe, V, Aínsa, JA, Velázquez-Campoy, A, Schaible, UE, Mamat, U & Sancho, J 2024, 'L-Thyroxine and L-thyroxine-based antimicrobials against Streptococcus pneumoniae and other Gram-positive bacteria', Heliyon, Jg. 10, Nr. 7, S. e27982. https://doi.org/10.1016/j.heliyon.2024.e27982
2023
Dal, N-JK, Schäfer, G, Thompson, AM, Schmitt, S, Redinger, N, Alonso-Rodriguez, N, Johann, K, Ojong, J, Wohlmann, J, Best, A, Koynov, K, Zentel, R, Schaible, UE, Griffiths, G, Barz, M & Fenaroli, F 2023, 'Π-Π interactions stabilize PeptoMicelle-based formulations of Pretomanid derivatives leading to promising therapy against tuberculosis in zebrafish and mouse models', JOURNAL OF CONTROLLED RELEASE, Jg. 354, S. 851-868. https://doi.org/10.1016/j.jconrel.2023.01.037
Horch, R, Rasp, D, Dietz, A, Ebbert, R, Steinmann, J, Schaible, UE, Mamat, U & Bertram, R 2023, 'tet-Dependent Gene Expression in Stenotrophomonas maltophilia', Microbiology spectrum, Jg. 11, Nr. 4, S. e0157623. https://doi.org/10.1128/spectrum.01576-23
Mamat, U, Hein, M, Grella, D, Taylor, CS, Scholzen, T, Alio, I, Streit, WR, Huedo, P, Coves, X, Conchillo-Solé, O, Gómez, A-C, Gibert, I, Yero, D & Schaible, UE 2023, 'Improved mini-Tn7 Delivery Plasmids for Fluorescent Labeling of Stenotrophomonas maltophilia', APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Jg. 89, Nr. 6, S. e0031723. https://doi.org/10.1128/aem.00317-23
Marriott, I, Khan, IA & Schaible, UE 2023, 'Insights in microbial immunology: 2022', FRONTIERS IN IMMUNOLOGY, Jg. 14, S. 1219083. https://doi.org/10.3389/fimmu.2023.1219083
Ojong, J 2023, 'Influence of Alterations in Iron Metabolism on Anti-mycobacterial Host Defense'.
Rudolph, D, Redinger, N, Schwarz, K, Li, F, Hädrich, G, Cohrs, M, Dailey, LA, Schaible, UE & Feldmann, C 2023, 'Amorphous Drug Nanoparticles for Inhalation Therapy of Multidrug-Resistant Tuberculosis', ACS nano, Jg. 17, Nr. 10, S. 9478-9486. https://doi.org/10.1021/acsnano.3c01664
Rutschmann, M, Redinger, N, Schaible, UE & Feldmann, C 2023, 'Amikacin@SiO2 core@shell nanocarriers to treat pulmonal bacterial infections', Journal of materials chemistry. B, Jg. 11, Nr. 24, S. 5460-5468. https://doi.org/10.1039/d2tb02609k
Schick, J, Altunay, M, Lacorcia, M, Marschner, N, Westermann, S, Schluckebier, J, Schubart, C, Bodendorfer, B, Christensen, D, Alexander, C, Wirtz, S, Voehringer, D, da Costa, CP & Lang, R 2023, 'IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity', eLife, Jg. 12, e72923. https://doi.org/10.7554/eLife.72923
2022
Behera, A, Jain, P, Ganguli, G, Biswas, M, Padhi, A, Pattanaik, KP, Nayak, B, Ergün, S, Hagens, K, Redinger, N, Saqib, M, Mishra, BB, Schaible, UE, Karnati, S & Sonawane, A 2022, 'Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , Jg. 23, Nr. 5, 2584. https://doi.org/10.3390/ijms23052584
Brandenburg, J, Heyckendorf, J, Marwitz, F, Zehethofer, N, Linnemann, L, Gisch, N, Karaköse, H, Reimann, M, Kranzer, K, Kalsdorf, B, Sanchez-Carballo, P, Weinkauf, M, Scholz, V, Malm, S, Homolka, S, Gaede, KI, Herzmann, C, Schaible, UE, Hölscher, C, Reiling, N & Schwudke, D 2022, 'Tuberculostearic Acid-Containing Phosphatidylinositols as Markers of Bacterial Burden in Tuberculosis', ACS infectious diseases, Jg. 8, Nr. 7, S. 1303-1315. https://doi.org/10.1021/acsinfecdis.2c00075
Dallenga, T, Linnemann, L & Schaible, UE 2022, 'Evaluation of Myeloperoxidase as Target for Host-Directed Therapy in Tuberculosis In Vivo', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , Jg. 23, Nr. 5, S. 2554. https://doi.org/10.3390/ijms23052554
Gómez, A-C, Lyons, T, Mamat, U, Yero, D, Bravo, M, Daura, X, Elshafee, O, Brunke, S, Gahan, CGM, O'Driscoll, M, Gibert, I & O'Sullivan, TP 2022, 'Synthesis and evaluation of novel furanones as biofilm inhibitors in opportunistic human pathogens', EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , Jg. 242, S. 114678. https://doi.org/10.1016/j.ejmech.2022.114678
Mrochen, DM, Miebach, L, Skowski, H, Bansemer, R, Drechsler, CA, Hofmanna, U, Hein, M, Mamat, U, Gerling, T, Schaible, U, von Woedtke, T & Bekeschus, S 2022, 'Toxicity and virucidal activity of a neon-driven micro plasma jet on eukaryotic cells and a coronavirus', Free radical biology & medicine, Jg. 191, S. 105-118. https://doi.org/10.1016/j.freeradbiomed.2022.08.026
Scior, T., Garcia-Hernandez, J.C., Abdallah H.H., Christian Alexander, C. 2022, 'QSAR Applied to 4-Chloro-3-formylcoumarin Derivatives Targeting Human Thymidine Phosphorylase: -', Clinical Complementary Medicine and Pharmacology, Jg. 2, Nr. 2, DOI: https://doi.org/10.1016/j.ccmp.2022.100031, S. 1-11. https://doi.org/10.1016/j.ccmp.2022.100031
von Woedtke, T, Gabriel, G, Schaible, UE & Bekeschus, S 2022, 'Oral SARS-CoV-2 reduction by local treatment: A plasma technology application?', Plasma processes and polymers (Print), S. e2200196. https://doi.org/10.1002/ppap.202200196
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