{"id":5428,"date":"2019-09-11T16:14:56","date_gmt":"2019-09-11T14:14:56","guid":{"rendered":"https:\/\/www.resist-cluster.de\/?page_id=5428"},"modified":"2025-09-24T15:22:37","modified_gmt":"2025-09-24T13:22:37","slug":"project-c2","status":"publish","type":"page","link":"https:\/\/www.resist-cluster.de\/en\/research\/project-area-c\/project-c2\/","title":{"rendered":"Project C2"},"content":{"rendered":"

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Which individual human factors favour the formation of biofilms?<\/h1><\/div>

Prof. F\u00f6rster\u00a0 |\u00a0 Prof. H\u00e4u\u00dfler\u00a0 |\u00a0 Prof. Stiesch\u00a0 |\u00a0 Dr. Wei\u00df<\/a><\/p><\/h2><\/div>

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What is this research project about?<\/span><\/h1><\/div>
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Scanning electronic image of a macrophage (red) and the bacterium Pseudomonas aeruginosa<\/em> (blue). \u00a9 Prof. Manfred Rohde, Dr. Sebastian Felgner<\/p>\n<\/div>

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What is this research project about?<\/h1><\/div>

Implant-associated infections represent a serious health burden in the clinics. They are the consequence of microorganisms that are able to colonise biological surfaces or surfaces of indwelling medical devices, and to form biofilms there. Biofilms are communities of microorganisms attached to such hydrated interfaces and enclosed in self-produced extracellular matrices. These structures present a considerable therapeutic challenge. Bacteria in biofilms exhibit altered phenotypes in their growth rates, gene expression profiles, and protein production. Embedded in their extracellular matrix, they become resilient to both antibiotics and the effector mechanisms of the immune system of the host. Since antibiotics treatment alone is apparently ineffective to treat these infections, the only possible treatment is the removal of the infected device followed by antibiotics. All of which results in high costs for both the patients and the healthcare facilities.<\/p>\n<\/div>

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Made visible with immunofluorescence staining: cell nuclei (blue), macrophages (red)<\/p>\n<\/div>

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and Pseudomonas aerugina<\/em> (green). \u00a9 Dr. Sebastian Felgner<\/p>\n<\/div>

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What’s the current status?<\/h1><\/div>
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The connections between the formation of bacterial biofilms on implants and the immune system of the host have not been investigated in detail. Thus, still little is known on the role of the immune system in the development of implant-associated biofilms produced by S. aureus or P. aeruginosa or other pathogenic bacteria. However, for rational design of treatment strategies, this would be an essential asset.<\/p>\n

To develop a mouse model for studying implant-associated infections, we pre-colonized osmotic pumps with S. aureus and implanted them subcutaneously into C57Bl\/6 mice. The bacteria expressed a bacterial luciferase which allowed monitoring of their expansion and the development of biofilms by employing noninvasive in vivo imaging. Subsequently, the presence of bacterial aggregates and biofilms on the surface of the implants was showed by immunofluorescence and electron microscopy. Additionally, myeloid cells, including neutrophils and monocytes, had been attracted to the colonized pumps and formed a barrier for the bacteria towards the tissue surrounding the implant. Despite the close neighborhood of bacteria and myeloid cells, no phagocytosis had taken place. Only containment of bacteria to the pumps could be observed. However, activation of myeloid cells had taken place. Depletion of neutrophils led to an enhanced infection and to dissemination of the bacteria from the pumps to the neighboring tissue.<\/p>\n<\/div>

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Under the microscope: skin samples with Staphylococcus<\/em><\/p>\n<\/div>

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aureus<\/em> within cellular traps (arrows).<\/p>\n<\/div>

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Immunofluorescence staining: Pseudomonas aeruginosa<\/em> bacteria whose flagella are stained green. \u00a9 Dr. Sebastian Felgner<\/p>\n<\/div>

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What are the project goals?<\/h1><\/div>

Our previous experiments using osmotic pumps loaded with immune modulating agents demonstrated that biofilm formation by bacterial pathogens like S. aureus can be influenced by manipulating the myeloid cells attracted to the colonized devices. First, these findings should be expanded to other biofilm forming bacterial pathogens. Therefore, the general objective of this proposal is to characterize the attracted myeloid cells as well as the biofilm residing bacteria in great detail. The phenotype of such myeloid cells, which is most likely of inflammatory type, should then be modulated using the osmotic pumps as source of exogenously supplied agents. Similarly, deletion mutants of the bacteria as well as recombinant murine hosts should be employed to further acquire information on the biofilm residing bacteria and the possibility of modulation.<\/p>\n<\/div><\/div><\/div>

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How do we get there?<\/h1><\/div>
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Osmotic pumps will be exposed to bacterial cultures in order to pre-colonize the devices. The pumps will then be surgically administered subcutaneously to the mice and monitored for various time periods. A major technique to quantitate the bacteria in vivo will consist of non-invasive imaging of the bacteria. Thus, bacteria will be used that express the bacterial luciferase and can be detected within the living mouse using the IVIS systems. Plating under these circumstances will not provide valid data since we have noticed that part of the bacteria might be lost when the pumps are removed from the animals. On the other hand, non-invasive imaging allows following expansion or reduction of the number of bacteria on the device in real time and data can be acquired from the same individual mouse over time. The IVIS will also be employed to quantitate the bacteria under antibiotic therapy. The bacteria should be resilient against treatment since a mature biofilm should be protective. Modulated biofilms might be less protective. This would provide a simple read out system for our experiments. Analysis will also employ microscopic examination of the colonized pumps using light sheet a well as scanning electron microscopy. The latter will provide high resolution pictures while for light sheet microscopy biofilms can be stained using fluorescent antibodies against components of the biofilm or against the bacteria.<\/p>\n<\/div>

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Under the microscope: surface of osmotic pumps, the anti-S. aureus antibodies are shown in green.<\/p>\n<\/div>

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Scanning electron microscopy of colonized implant surfaces.<\/p>\n<\/div>

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Images modified by https:\/\/doi.org\/10.3389\/fimmu.2019.01082 \u00a9 by the authors.<\/p>\n<\/div>

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Mouse model for implant-associated infections.<\/p>\n<\/div>

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Projectleaders<\/h1><\/div>

Project title: Identifying host factors that drive biofilm formation<\/h4><\/div>
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Prof. Dr. Reinhold F\u00f6rster<\/h3><\/div>

Projects: B5<\/a>, B9<\/a>, C2<\/a><\/h3><\/div>
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CV & VIDEO<\/span><\/a><\/div>
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Prof. Dr. Susanne H\u00e4u\u00dfler<\/h3><\/div>

Projects: C1<\/a>, C2<\/a><\/h3><\/div>
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CV & Contact<\/span><\/a><\/div>
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Prof. Dr. Meike Stiesch<\/h3><\/div>

Projects: C1<\/a>, C2<\/a><\/h3><\/div>
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CV & Contact<\/span><\/a><\/div>
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Project C2 Publications<\/h1><\/div>

Publications 2025
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(p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms<\/strong><\/a> F. Engelhardt, K. Turnbull, M. G\u00fcr, M. M\u00fcsken, M. Preusse, S. H\u00e4ussler, et al. NPJ Biofilms Microbiomes<\/strong> 2025 Vol. 11 Issue 1 Pages 148 Accession Number: 40750589 PMCID: PMC12316884 DOI: 10.1038\/s41522-025-00795-7<\/p>\n

The Submucosal Microbiome Correlates with Peri-implantitis Severity – PubMed<\/a><\/strong> A. A. Joshi, S. P. Szafra\u0144ski, M. Steglich, I. Yang, W. Behrens, P. Schaefer-Dreyer, et al. J Dent Res<\/strong> 2025 Pages 220345251352809 Accession Number: 40719760 DOI: 10.1177\/00220345251352809<\/p>\n

Integrative microbiome- and metatranscriptome-based analyses reveal diagnostic biomarkers for peri-implantitis<\/strong><\/a> A. A. Joshi, S. P. Szafra\u0144ski, M. Steglich, I. Yang, T. Qu, P. Schaefer-Dreyer, et al. NPJ Biofilms Microbiomes<\/strong> 2025 Vol. 11 Issue 1 Pages 175 Accession Number: 40858628 DOI: 10.1038\/s41522-025-00807-6<\/p>\n

Uncovering Risk Factors of Premature Mortality in Common Variable Immunodeficiency<\/strong><\/a> P. Bez, B. Smits, C. Geier, A. Hirsch, A. Caballero de Oyteza, M. Proietti, et al. J Allergy Clin Immunol Pract<\/strong> 2025 Vol. 13 Issue 5 Pages 1201-1209.e10 Accession Number: 40090481 DOI: 10.1016\/j.jaip.2025.03.009<\/p>\n

Establishment and characterization of persistent Pseudomonas aeruginosa infections in air-liquid interface cultures of human airway epithelial cells<\/strong><\/a> S. Bouheraoua, S. Cleeves, M. Preusse, M. M\u00fcsken, P. Braubach, M. Fuchs, et al. Infect Immun 2025<\/strong> Pages e0060324 Accession Number: 39964154 DOI: 10.1128\/iai.00603-24<\/p>\n

Publications 2023<\/strong><\/p>\n

The Origin of the Intracellular Silver in Bacteria: A Comprehensive Study using Targeting Gold-Silver Alloy Nanoparticles.<\/strong><\/a> Streich C, Stein F, Jakobi J, Ingendoh-Tsakmakidis A, Heine N, Rehbock C, Winkel A, Grade S, K\u00fchnel M, Migunov V, Kov\u00e1cs A, Knura T, Stiesch M, Sures B, Barcikowski S. Adv Healthc Mater. 2023 Dec;12(30):e2302084. Epub 2023 Sep 17.<\/p>\n

Transcriptome Dynamics of Pseudomonas aeruginosa during Transition from Overlapping To Non-Overlapping Cell Cycles.<\/strong><\/a> Alpers K, Vatareck E, Gr\u00f6be L, M\u00fcsken M, Scharfe M, H\u00e4ussler S, Tomasch J. mSystems. 2023 Apr 27;8(2):e0113022. Epub 2023 Feb 14.<\/p>\n

Publications 2022<\/strong><\/p>\n

Dual Effect: High NADH Levels Contribute to Efflux-Mediated Antibiotic Resistance but Drive Lethality Mediated by Reactive Oxygen Species<\/strong> <\/a>A. Arce-Rodr\u00edguez, D. Pankratz, M. Preusse, P. I. Nikel and S. H\u00e4usslermBio 2022 <\/strong>Vol. 13 Issue 1 Pages e0243421 DOI: 10.1128\/mbio.02434-21<\/p>\n

Antibacterial and Cytocompatible: Combining Silver Nitrate with Strontium Acetate Increases the Therapeutic Window.<\/strong><\/a>\u00a0Parizi MK, Doll K, Rahim MI, Mikolai C, Winkel A, Stiesch M.\u00a0 Int J Mol Sci. 2022 Jul 22;23(15):8058. doi: 10.3390\/ijms23158058. PMID: 35897634; PMCID: PMC9331456.<\/p>\n

The membrane-active polyaminoisoprenyl compound NV716 re-sensitizes Pseudomonas aeruginosa to antibiotics and reduces bacterial virulence.<\/strong><\/a>\u00a0Wang G, Brunel JM, Preusse M, Mozaheb N, Willger SD, Larrouy-Maumus G, Baatsen P, H\u00e4ussler S, Bolla JM, Van Bambeke F. Commun Biol. 2022 Aug 25;5(1):871. doi: 10.1038\/s42003-022-03836-5. PMID: 36008485; PMCID: PMC9411590.<\/p>\n

Publications 2021<\/strong><\/p>\n

The effect of keratinized mucosa on the severity of peri-implant mucositis differs between periodontally healthy subjects and the general population: a cross-sectional study.<\/strong><\/a>\u00a0Kabir L, Stiesch M, Grischke J.\u00a0 Clin Oral Investig. 2021 Mar;25(3):1183-1193. doi: 10.1007\/s00784-020-03422-1. Epub 2020 Jul 1. PMID: 32607828; PMCID: PMC7878216.<\/p>\n

The human oral phageome.<\/strong><\/a>\u00a0Szafra\u0144ski SP, Slots J, Stiesch M.\u00a0 Periodontol 2000. 2021 Jun;86(1):79-96. doi: 10.1111\/prd.12363. Epub 2021 Mar 10. PMID: 33690937.<\/p>\n

Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory<\/strong><\/a> T\u00a0cells T. Strowig and J. Huehn Immunity 2021 Vol. 54 Issue 4 Pages 702-720.e17 DOI: 10.1016\/j.immuni.2021.03.007<\/p>\n

Analysis of the organization and expression patterns of the convergent Pseudomonas aeruginosa lasR\/rsaL gene pair uncovers mutual influence<\/strong><\/a> S. Schinner, M. Preusse, C. Kesthely and S. H\u00e4ussler Molecular Microbiology<\/strong> 2021 Vol. 115 Issue 4 Pages 643-657 DOI: 10.1111\/mmi.14628<\/p>\n

Publications 2020<\/strong><\/p>\n

Early host-microbe interaction in a peri-implant oral mucosa-biofilm model.<\/strong><\/a>\u00a0Mikolai C, Kommerein N, Ingendoh-Tsakmakidis A, Winkel A, Falk CS, Stiesch M. Cell Microbiol. 2020 Aug;22(8):e13209. doi: 10.1111\/cmi.13209. Epub 2020 May 14. PMID: 32329166.<\/p>\n

Evidence for inoculum size and gas interfaces as critical factors in bacterial biofilm formation on magnesium implants in an animal model.<\/strong><\/a>\u00a0Rahim MI, Szafra\u0144ski SP, Ingendoh-Tsakmakidis A, Stiesch M, Mueller PP. Colloids Surf B Biointerfaces. 2020 Feb;186:110684. doi: 10.1016\/j.colsurfb.2019.110684. Epub 2019 Nov 28. PMID: 31812076.<\/p>\n

Publications 2019<\/strong><\/p>\n

IL-1\u03b2 Promotes Staphylococcus aureus<\/em> Biofilms on Implants in vivo.<\/strong><\/a> Gutierrez Jauregui R, Fleige H, Bubke A, Rohde M, Weiss S, F\u00f6rster R. Front Immunol. 2019 May 17;10:1082. eCollection 2019.<\/p>\n

Establishment of an induced memory response in Pseudomonas aeruginosa during infection of a eukaryotic host.<\/strong><\/a>\u00a0Kordes A, Grahl N, Koska M, Preusse M, Arce-Rodriguez A, Abraham WR, Kaever V, H\u00e4ussler S. ISME J. 2019 Aug;13(8):2018-2030. doi: 10.1038\/s41396-019-0412-1. Epub 2019 Apr 5. PMID: 30952997; PMCID: PMC6775985.<\/p>\n

Keratinized mucosa width is associated with severity of peri-implant mucositis. A cross-sectional study.<\/strong><\/a>\u00a0Jasmin Grischke, Annika Karch, Andreas Wenzlaff, Magdalena Marta Foitzik, Meike Stiesch, J\u00f6rg Eberhard. Clinical Oral Implants Research. First published: 10 April 2019. https:\/\/doi.org\/10.1111\/clr.13432<\/p>\n

Genetically diverse Pseudomonas aeruginosa populations display similar transcriptomic profiles in a cystic fibrosis explanted lung.<\/strong>\u00a0<\/a>Kordes A, Preusse M, Willger SD, Braubach P, Jonigk D, Haverich A, Warnecke G, H\u00e4ussler S.\u00a0 Nat Commun. 2019 Jul 30;10(1):3397. doi: 10.1038\/s41467-019-11414-3. PMID: 31363089; PMCID: PMC6667473.<\/p>\n<\/div>

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Publications of the Project C2<\/h1><\/div>
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