2-2020-1376

New Chemiluminescent Protease Probe for Rapid, Sensitive, and Inexpensive Detection of Live Mycobacterium tuberculosis

Tuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment is often limited by insufficient diagnostic capabilities, especially at the point of care in low-resource settings. The ideal diagnostic must be fast, be cheap, and require minimal clinical resources while providing high sensitivity, selectivity, and the ability to differentiate live from dead bacteria.
OUR SOLUTION
• We developed a fast, luminescent, and affordable sensor of Hip1 (FLASH) for detecting and monitoring drug susceptibility of Mycobacterium tuberculosis (Mtb). The key ability of the CL probe is its high detection sensitivity for TB
• FLASH is a selective chemiluminescent substrate for the Mtb protease Hip1 that, when processed, produces visible light that can be measured with a high signal-to-noise ratio using inexpensive sensors
• FLASH is sensitive to fmol of recombinant Hip1 enzyme in vitro and can detect as few as thousands of Mtb cells in culture or in human sputum samples within minutes
• The probe is highly selective for Mtb compared to other nontuberculous mycobacteria and can distinguish live from dead cells
• FLASH can be used to measure antibiotic killing of Mtb in culture with greatly accelerated timelines compared to traditional protocols
• FLASH has the potential to enhance both TB diagnostics and drug resistance monitoring in resource-limited settings.

STATUS
In vitro testing utilizing bacteria cultures

INTELLECTUAL PROPERTY
PCT was submitted in Feb 2021: PCT/IL2021/050184

REFERENCES
Chemiluminescent Protease Probe for Rapid, Sensitive, and Inexpensive Detection of Live Mycobacterium tuberculosis Brett M. Babin, Gabriela Fernandez-Cuervo, Jessica Sheng, Ori Green, Alvaro A. Ordonez, Mitchell L. Turner, Laura J. Keller, Sanjay K. Jain, Doron Shabat, and Matthew Bogyo. ACS Central Science 2021 7 (5), 803-814

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