How can a precise characterisation of microbial communities result in the development of new strategies against biofilm-associated infections?

What is this research project about?

Figures 1 | Scientific concept of the C1 research project

What is this research project about?

Bacteria in biofilms are embedded in a self-produced extracellular matrix and exhibit an increased resistance to adverse conditions. In the human host, biofilm bacteria are responsible for persistent infections and efficiently withstand antibiotic treatment and the host immune response. Once a bacterial biofilm infection is established it becomes very difficult to eradicate, even in the absence of genotypic resistance. Biofilm infections affect millions of people and every year chronic infections in patients due to biofilm formation are a multi-billion Euro burden to national healthcare systems. With progress of medical sciences, more and more indwelling devices for the purpose of medical treatments and foreign body implants are applied. Infection continues to be a major complication of their use. Also, there are biofilm infections not associated with foreign bodies, such as chronic infections of the lungs of cystic fibrosis patients and of patients with chronic obstructive pulmonary diseases. Ongoing inflammation and changes in the structure and function of the affected tissue largely determine morbidity and mortality in these patients.

Figure 1: There is a lack of treatment options for Biofilm-associated infections. We want to identify biomarkers whose presence is correlated with the resistance of the P. aeruginosa biofilm and genetic / metabolic patterns and which characterize the switch to the establishment of pathogenic biofilms on implants (C1.2). This will serve to develop a diagnostic tool for biofilm resistance and disease excitationProfi ling (C1.3) and innovative treatment strategies targeting biofilm resistance mechanisms (C1.4).

Figures 2-4 | Biofilms of clinical idolates of Pseudomonas aeruginosa, living cells are green, dead cells are red. Source: TWINCORE / Jann Thöming

What’s the current status?

Although chronic biofilm-associated infections have been extensively studied, there are many open questions and the general recalcitrance of biofilm-grown bacteria is only incompletely understood. The successful use of antibiotics to eradicate biofilm-associated infection relies on our ability to overcome several main problems. First, for a more targeted anti-biofilm therapy, knowledge on the biofilm-specific resistance profile of individual bacterial isolates is essential, as well as knowledge on when natural colonizing bacterial communities transition to pathogenic biofilms e.g. on implants. In addition, new therapy options will have to be developed to overcome the second limitation of current treatment, which is the general recalcitrance of biofilm populations.

What are the project goals?

The combination of detailed information of the infecting pathogens with advanced phenotypic and genotypic profiling methodologies holds considerable promise for improving strategies to combat chronic biofilm-associated infections. Knowledge on etiological mechanisms underlying the evolution of biofilm resistance has the promise to change the way physicians treat chronic infections. This work is undertaken with the view to address a critical unmet medical need and to provide the necessary conditions to develop effective individualized diagnostic and therapeutic intervention strategies for the control of biofilm-associated infections.

How do we get there?

Our research groups have established extensive expertise in the analysis of the structure, assembly and microbiological diversity of medical biofilms, and have applied methodologies including DNA/RNA sequencing and machine learning approaches to describe the genomic and transcriptional landscape of infecting pathogens in vitro and ex vivo. Within RESIST we want to transfer gained knowledge and experience from our work on bacterial biofilms and establish a genome-based prediction of bacterial phenotypes by integrating complex OMICS-data also using machine learning classifiers, phylogenomic clustering and feature selection techniques.

Projectleaders

Project title: Biofilm Profling

Prof. Dr. Alice McHardy

Projekt: B2, B10, C1

CV & Contact

Prof. Dr. Susanne Häußler

Projekte: C1, C2

CV & Contact

Prof. Dr. Meike Stiesch

Projekte: C1, C2

CV & Contact

Project C1 Publications

You will find project related publications here.

  1. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, Scheible R, Rusch S, Gasteiger LM, Grimbacher B, Mahlaoui N, Ehl S; ESID Registry Working Party and collaborators. J Allergy Clin Immunol Pract. 2019 Jul – Aug;7(6):1763-1770. doi: 10.1016/j.jaip.2019.02.004. Epub 2019 Feb 15.
  2. Evaluating laboratory criteria for combined immunodeficiency in adult patients diagnosed with common variable immunodeficiency. von Spee-Mayer C, Koemm V, Wehr C, Goldacker S, Kindle G, Bulashevska A, Proietti M, Grimbacher B, Ehl S, Warnatz K. Clin Immunol. 2019 Jun;203:59-62. doi: 10.1016/j.clim.2019.04.001. Epub 2019 Apr 17.
  3. Assessing the Functional Relevance of Variants in the IKAROS Family Zinc Finger Protein 1 (IKZF1) in a Cohort of Patients With Primary Immunodeficiency. Eskandarian Z, Fliegauf M, Bulashevska A, Proietti M, Hague R, Smulski CR, Schubert D, Warnatz K, Grimbacher B. Front Immunol. 2019 Apr 16;10:568. doi: 10.3389/fimmu.2019.00568. eCollection 2019. Erratum in: Front Immunol. 2019 Jun 28;10:1490.
  4. Corrigendum: Assessing the Functional Relevance of Variants in the IKAROS Family Zinc Finger Protein 1 (IKZF1) in a Cohort of Patients With Primary Immunodeficiency. Eskandarian Z, Fliegauf M, Bulashevska A, Proietti M, Hague R, Smulski CR, Schubert D, Warnatz K, Grimbacher B. Front Immunol. 2019 Jun 28;10:1490. doi: 10.3389/fimmu.2019.01490. eCollection 2019.
  5. The German National Registry of Primary Immunodeficiencies (2012-2017). El-Helou SM, Biegner AK, Bode S, Ehl SR, Heeg M, Maccari ME, Ritterbusch H, Speckmann C, Rusch S, Scheible R, Warnatz K, Atschekzei F, Beider R, Ernst D, Gerschmann S, Jablonka A, Mielke G, Schmidt RE, Schürmann G, Sogkas G, Baumann UH, Klemann C, Viemann D, von Bernuth H, Krüger R, Hanitsch LG, Scheibenbogen CM, Wittke K, Albert MH, Eichinger A, Hauck F, Klein C, Rack-Hoch A, Sollinger FM, Avila A, Borte M, Borte S, Fasshauer M, Hauenherm A, Kellner N, Müller AH, Ülzen A, Bader P, Bakhtiar S, Lee JY, Heß U, Schubert R, Wölke S, Zielen S, Ghosh S, Laws HJ, Neubert J, Oommen PT, Hönig M, Schulz A, Steinmann S, Schwarz K, Dückers G, Lamers B, Langemeyer V, Niehues T, Shai S, Graf D, Müglich C, Schmalzing MT, Schwaneck EC, Tony HP, Dirks J, Haase G, Liese JG, Morbach H, Foell D, Hellige A, Wittkowski H, Masjosthusmann K, Mohr M, Geberzahn L, Hedrich CM, Müller C, Rösen-Wolff A, Roesler J, Zimmermann A, Behrends U, Rieber N, Schauer U, Handgretinger R, Holzer U, Henes J, Kanz L, Boesecke C, Rockstroh JK, Schwarze-Zander C, Wasmuth JC, Dilloo D, Hülsmann B, Schönberger S, Schreiber S, Zeuner R, Ankermann T, von Bismarck P, Huppertz HI, Kaiser-Labusch P, Greil J, Jakoby D, Kulozik AE, Metzler M, Naumann-Bartsch N, Sobik B, Graf N, Heine S, Kobbe R, Lehmberg K, Müller I, Herrmann F, Horneff G, Klein A, Peitz J, Schmidt N, Bielack S, Groß-Wieltsch U, Classen CF, Klasen J, Deutz P, Kamitz D, Lassay L, Tenbrock K, Wagner N, Bernbeck B, Brummel B, Lara-Villacanas E, Münstermann E, Schneider DT, Tietsch N, Westkemper M, Weiß M, Kramm C, Kühnle I, Kullmann S, Girschick H, Specker C, Vinnemeier-Laubenthal E, Haenicke H, Schulz C, Schweigerer L, Müller TG, Stiefel M, Belohradsky BH, Soetedjo V, Kindle G, Grimbacher B. Front Immunol. 2019 Jul 19;10:1272. doi: 10.3389/fimmu.2019.01272. eCollection 2019.
  6. The architecture of the IgG anti-carbohydrate repertoire in primary antibody deficiencies. Jandus P, Boligan KF, Smith DF, de Graauw E, Grimbacher B, Jandus C, Abdelhafez MM, Despont A, Bovin N, Simon D, Rieben R, Simon HU, Cummings RD, von Gunten S. Blood. 2019 Nov 28;134(22):1941-1950. doi: 10.1182/blood.2019001705.
  7. Distinct molecular response patterns of activating STAT3 mutations associate with penetrance of lymphoproliferation and autoimmunity. Jägle S, Heeg M, Grün S, Rensing-Ehl A, Maccari ME, Klemann C, Jones N, Lehmberg K, Bettoni C, Warnatz K, Grimbacher B, Biebl A, Schauer U, Hague R, Neth O, Mauracher A, Pachlopnik Schmid J, Fabre A, Kostyuchenko L, Führer M, Lorenz MR, Schwarz K, Rohr J, Ehl S. Clin Immunol. 2019 Nov 23;210:108316. doi: 10.1016/j.clim.2019.108316.
  8. Late-Onset Antibody Deficiency Due to Monoallelic Alterations in NFKB1. Schröder C, Sogkas G, Fliegauf M, Dörk T, Liu D, Hanitsch LG, Steiner S, Scheibenbogen C, Jacobs R, Grimbacher B, Schmidt RE, Atschekzei F. Front Immunol. 2019 Nov 14;10:2618. doi: 10.3389/fimmu.2019.02618. eCollection 2019.
  9. Structural Noninfectious Manifestations of the Central Nervous System in Common Variable Immunodeficiency Disorders. van de Ven A, Mader I, Wolff D, Goldacker S, Fuhrer H, Rauer S, Grimbacher B, Warnatz K. J Allergy Clin Immunol Pract. 2019 Dec 16. pii: S2213-2198(19)31026-8. doi: 10.1016/j.jaip.2019.11.039.
  10. Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. Tesch VK, Abolhassani H, Shadur B, Zobel J, Mareika Y, Sharapova S, Karakoc-Aydiner E, Rivière JG, Garcia-Prat M, Moes N, Haerynck F, Gonzales-Granado LI, Santos Pérez JL, Mukhina A, Shcherbina A, Aghamohammadi A, Hammarström L, Dogu F, Haskologlu S, İkincioğulları AI, Bal SK, Baris S, Kilic SS, Karaca NE, Kutukculer N, Girschick H, Kolios A, Keles S, Uygun V, Stepensky P, Worth A, van Montfrans JM, Peters AM4, Meyts I, Adeli M, Marzollo A, Padem N, Khojah AM, Chavoshzadeh Z, Stefanija MA, Bakhtiar S, Florkin B, Meeths M, Gamez L, Grimbacher B, Seppänen MR, Lankester A, Gennery AR, Seidel MG; Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation (EBMT) and the European Society of Immunodeficiencies (ESID). J Allergy Clin Immunol. 2019 Dec 27. pii: S0091-6749(19)32603-X. doi: 10.1016/j.jaci.2019.12.896.

Project C1
Publications