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Quorum-Quenching Human Designer Cells for Closed-Loop Control of Pseudomonas aeruginosa Biofilms

Sedlmayer, Ferdinand and Jaeger, Tina and Jenal, Urs and Fussenegger, Martin. (2017) Quorum-Quenching Human Designer Cells for Closed-Loop Control of Pseudomonas aeruginosa Biofilms. Nano Letters, 17 (8). pp. 5043-5050.

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Official URL: https://edoc.unibas.ch/59164/

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Abstract

Current antibiotics gradually lose their efficacy against chronic Pseudomonas aeruginosa infections due to development of increased resistance mediated by biofilm formation, as well as the large arsenal of microbial virulence factors that are coordinated by the cell density-dependent phenomenon of quorum sensing. Here, we address this issue by using synthetic biology principles to rationally engineer quorum-quencher cells with closed-loop control to autonomously dampen virulence and interfere with biofilm integrity. Pathogen-derived signals dynamically activate a synthetic mammalian autoinducer sensor driving downstream expression of next-generation anti-infectives. Engineered cells were able to sensitively score autoinducer levels from P. aeruginosa clinical isolates and mount a 2-fold defense consisting of an autoinducer-inactivating enzyme to silence bacterial quorum sensing and a bipartite antibiofilm effector to dissolve the biofilm matrix. The self-guided cellular device fully cleared autoinducers, potentiated bacterial antibiotic susceptibility, substantially reduced biofilms, and alleviated cytotoxicity to lung epithelial cells. We believe this strategy of dividing otherwise coordinated pathogens and breaking up their shielded stronghold represents a blueprint for cellular anti-infectives in the postantibiotic era.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development
05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Jenal)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Molecular Microbiology (Jenal)
05 Faculty of Science > Departement Biozentrum > Infection Biology
UniBasel Contributors:Jenal, Urs
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:1530-6984
e-ISSN:1530-6992
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:04 Jul 2018 12:31
Deposited On:04 Jul 2018 12:31

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