PT  - JOURNAL ARTICLE
AU  - M. Kamariza
AU  - P. Shieh
AU  - F. P. Rodriguez-Rivera
AU  - C. S. Ealand
AU  - B. Chu
AU  - N. Martinson
AU  - B. D. Kana
AU  - C. R. Bertozzi
TI  - Detection of live mycobacteria with a solvatochromic trehalose probe for point-of-care tuberculosis diagnosis
AID  - 10.1101/171553
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 171553
4099  - http://biorxiv.org/content/early/2017/08/02/171553.short
4100  - http://biorxiv.org/content/early/2017/08/02/171553.full
AB  - Tuberculosis (TB) is the leading cause of death from an infectious bacterial disease. Poor diagnostic tools to detect active disease plague TB control programs and affect patient care. Accurate detection of live Mycobacterium tuberculosis (Mtb), the causative agent of TB, will improve TB diagnosis and patient treatment. We report that live mycobacteria can be specifically detected with a fluorogenic trehalose analog. We designed a 4-N,N-dimethylamino-1,8- naphthalimide-trehalose (DMN-Tre) conjugate that undergoes >700-fold fluorescence increase when transitioned from aqueous to hydrophobic environments. This enhancement occurs upon metabolic conversion of DMN-Tre to trehalose monomycolate and incorporation into the outer membrane. DMN-Tre labeling enabled the rapid, no-wash visualization of mycobacterial and corynebacterial species without nonspecific labeling of Gram-positive or –negative bacteria. DMN-Tre labeling was selective for live mycobacteria and was reduced by treatment with TB drugs. Lastly, DMN-Tre labeled Mtb in TB-positive sputum samples suggesting this operationally simple method may be deployable for TB diagnosis.