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  • Oral Presentation
  • OP-BSM-006

Engineering of a sticky therapeutic microbe

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Barbarossa Saal

Session

Biotechnology & Synthetic Microbiology 1

Thema

  • Biotechnology & Synthetic Microbiology

Mitwirkende

Alexandre Chamas (Jena / DE), Gerald Lackner (Jena / DE)

Abstract

Innovative strategies are needed in the permanent fight against microbial pathogenic infections. Utilization of antibiotics is limited by the spread of resistant strains, the slow rate of new antibiotics discoveries and the deleterious off-target effect of these antibiotics against our microbiome. Probiotic strains represent an appealing alternative to antibiotics but suffer from weak efficacy and a poorly understood mode of action. In an effort to combine the best of the two strategies, the concept of therapeutic microbes has been developed in the last years. Therapeutic microbes are commensal organisms genetically engineered to have an enhanced therapeutic effect and they can be designed to specifically combat a microbial pathogenic strain. Thanks to synthetic biology tools, these natural hosts of our microbiome can be tuned to produce bioactive molecules against a wide variety of pathogens in situ. For that purpose, they can be upgraded by the integration of genetic elements called modules allowing detection of a target or ensuring biocontrol of the modified organism. In our lab, we work on implementing a cell-cell adhesion module, i.e. allow the specific attachment of our therapeutic microbe to a microbial target. With this module, higher bioactive compound concentrations can be achieved near the target and the therapeutic potential of our microbe will be enhanced. In a first proof of principle experiment, we describe the engineering of an adhesion module for the specific binding of the probiotic Escherichia coli Nissle to the fungal pathogen Candida albicans. Through membrane display of diverse carbohydrate binding proteins, we can show tight adhesion of the bacteria to the fungi hyphae. Adhesion between two members of the microbiome would not only be interesting to treat microbial infections but could also help to better understand mutualistic or antagonistic relationships inside the microbiome. Moreover, alternative adhesion modules could be engineered to target abiotic surfaces or different parts of the human body, therefore opening the way for innovative medical applications.

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