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Biology subjects

Brasino, M.

Publications and source records attributed to Brasino, M..

2 recordsLinked to original sources

Mutation of the peptide-regulated transcription factor ComR for amidated peptide specificity and heterologous function in Lactiplantibacillus plantarum WCFS1

There is a growing interest in the use of probiotic bacteria as biosensors for the detection of disease. However, there is a lack of bacterial receptors developed for specific disease biomarkers. Here, we have investigated the use of the peptide-regulated transcription factor ComR from Streptococcus spp. for specific peptide biomarker detection. ComR exhibits a number of attractive features that are potentially exploitable to create an exquisitely sensitive biomolecular switch for engineered biosensor circuitry within the probiotic organism Lactiplantibacillus plantarum WCFS1. By screening a library of ComR mutant protein variants, we identified mutations that increased the specificity of ComR toward an amidated version of its cognate extracellular signaling peptide, demonstrating the potential for ComR to detect this important class of biomarker.

synthetic biology↗

Engineered Lactiplantibacillus plantarum as a Biosensor Probe for the Lungs

Lungs are a frequent site for disease but are difficult to image and probe, potentially exacerbating lung disease, delaying diagnoses and impacting survival. Here, we demonstrate a low cost, minimally invasive method to probe the lungs for disease, using genetically engineered Lactiplantibacillus plantarum strain WCFS1. Genetically modified WCFS1 was delivered specifically to the lungs of mice, where it was shown to remain transcriptionally active for several hours and then be cleared without further colonization. WCFS1 was further modified to secrete nanoluciferase as a synthetic biomarker, which traveled from the bacteria in the lung to the urine where it was easily detected. The administered bacteria also secreted nano-luciferase upon detecting a specific peptide secreted by a mouse lung cancer cell line in vitro or in vivo from syngeneic tumors.

synthetic biology↗