Projects Molekular Bacteriology

Projects Molekular Bacteriology

Targeting biofilm resistance

The proposed project is committed to develop innovative diagnostics and to strive for therapeutic solutions in patients suffering from biofilm-associated infections. The objective is to apply data-driven science in order to unlock the potential of microbial genomics. We will apply genome-wide association studies on an existing large sequence variation and gene expression dataset of a plethora of clinical Pseudomonas aeruginosa isolates that has been generated the last five years. New innovative treatment strategies that target biofilm resistance mechanisms to enhance the efficacy of current antibiotics will be validated and optimized in in vitro and in vivo biofilm models. Our approach does not only aim to provide a prediction of biofilm resistance based on the bacteria´s genotype but also to transform treatment paradigms for the management of chronic infections in order to combat biofilm-associated infections.

Publications

Molecular resistance profiling

In spite of the initial enthusiasm and the huge literature on their diagnostic use, gene-detection-based molecular methods have not yet had the dramatic impact on routine diagnostic microbiology that many predicted. We have established a rapid, cost-effective and robust molecular diagnostic assay for resistance profiling as well as geno-typing of underserved multi-drug resistant opportunistic gram-negative pathogens. Our RAPID (Rapid Antimicrobial susceptibility testing and Phylogenetic Identification) assay is a gene-detection-based high-density molecular system which tests for a plethora of genetic resistance determinants to provide timely information on resistance profiles as well as on bacterial genotypes. In order to further develop our RAPID system and to bring molecular resistance testing into clinical application, the diagnostic performance of our RAPID system will be evaluated in this project. This will necessitate the application of RAPID on a plethora of clinical isolates (>1000) that will be collected from different laboratories across Europe and also world-wide.

We will move from the assessment of the technical performance of RAPID system (phase I) to studies that aim at evaluating its diagnostic performance (sensitivity and specificity, phase II). Most importantly in the future it will be important to show that the use of the molecular resistance and clonal relatedness profiling will have an impact in the management of nosocomial infections.

Publications

Targeting biofilm resistance

Müsken M, DiFiore S, Römling U, Häussler S (2010) 96-well plate based optical method for the quantitative and qualitative evaluation of Pseudomonas aeruginosa biofilm formation and its application for susceptibility testing. Nat Protoc. 5:1460-9.

Blanka A, Düvel J, Dötsch A, Klinkert B, Abraham WR, Kaever V, Ritter C, Narberhaus F, Häussler S (2015) Constitutive production of c-di-GMP is associated with mutations in a variant of Pseudomonas aeruginosa with altered membrane composition. Science Signaling 14;8(372).

Bielecki P, Jensen V, Schulze W, Gödeke J, Strehmel J, Eckweiler D, Nicolai T, Bielecka A, Wille T, Gerlach RG, Häussler S (2015) Cross talk between the response regulators PhoB and TctD allows for the integration of diverse environmental signals in Pseudomonas aeruginosa. Nucleic Acids Res. 43(13):6413-25.

Molecular resistance profiling

Dötsch A, Schniederjans M, Khaledi A, Hornischer K, Schulz S, Bielecka A, Eckweiler D, Pohl S, Häussler S. (2015) The Pseudomonas aeruginosa transcriptional landscape is shaped by environmental heterogeneity and genetic variation. MBio 6(4):e00749

Schulz S, Eckweiler D, Bielecka A, Nicolai T, Franke R, Dötsch A, Hornischer K, Bruchmann S, Düvel J, Häussler S (2015) Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk. PLoS Pathog. 11(3):e1004744.

Pommerenke C, Müsken M, Becker T, Dötsch A, Overhage J, Klawonn F, Häussler S (2010) Global Phenotype-Genotype correlations in Pseudomonas aeruginosa. PLoS Pathog 26(3): pii: e1001074.