UCLA

Tuberculosis (TB) remains as the second leading infectious killer worldwide. In 2022 alone, 1.3 million people died from TB, with the disease being most prevalent in low-resource countries. In these settings with high TB prevalence, access to expensive diagnostic tools is limited, making the development of fast, sensitive, specific and low-cost diagnostic methods crucial. Here, we employ the 4-N,Ndimethylamino-1,8-naphthalimide–conjugated trehalose (DMN-Tre) and 3-Hydroxychromoneconjugated trehalose (3HC-Tre) solvatochromic trehalose conjugated fluorogenic dyes to probe the unique properties of mycobacteria and other Actinomycetales. These conjugates are incorporated into the mycomembrane as trehalose dimycolates, where they fluoresce upon contact with the hydrophobic environment of the mycomembrane. For these probes to facilitate faster diagnostics, they must specifically target mycobacteria, eliminating the requirement of extensive pre-processing of clinical samples. This thesis presents the results of specificity testing for both DMN-Tre and 3HC-Tre. Using flow cytometry, plate reader and microscopy, this research demonstrates that DMN-Tre exhibits specificity for mycobacteria. In contrast, 3HC-Tre demonstrated limited specificity. These findings suggest that DMN-Tre has the potential to be developed into a rapid, low-cost diagnostic tool for TB, tailored to the needs of resource-limited settings.