Designing humans to prevent biofilms

Taking advantage of synthetic biology, researchers have produced human cells that can produce a synthetic autoinducer.

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Jul 21, 2017
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Targeting virulence mechanisms of pathogens has become a hot area of research in the past few years. The idea is that you can reduce the severity of an infection without applying a strong selective pressure to develop resistance as you do with antibiotics. Common deliver approaches for these range from oral drugs to direct embedding into medical materials. 

A Swiss group took another approach. They asked, what if human cells produce their own anti-virulence defences? Read more about it below.

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

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.

Reference


Nano Lett. 2017 Jul 13. doi: 10.1021/acs.nanolett.7b02270. [Epub ahead of print]
Quorum-Quenching Human Designer Cells for Closed-Loop Control of Pseudomonas aeruginosa Biofilms.

Sedlmayer F, Jaeger T, Jenal U, Fussenegger M

Go to the profile of Ben Libberton

Ben Libberton

Postdoc and Public Information Officer, Karolinska Institute

I'm a researcher at the Swedish Medical Nanoscience Center in Stockholm and the Community Editor for npj Biofilms and Microbiomes. I'm interested in how bacteria cause disease and look to technology to produce novel tools to study and ultimately prevent infection. My research spans different disciplines from basic microbiology to surface chemistry and organic bioelectronics.

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