A Fluorogenic Trehalose Probe for Tracking Phagocytosed Mycobacterium tuberculosis.

Tingting Dai, Jinghang Xie, Qihua Zhu, Mireille Kamariza, Ke Jiang, Carolyn R Bertozzi, Jianghong Rao

Journal of the American Chemical Society 2020 Sep 09

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Tuberculosis (TB) disease is a global epidemic caused by the pathogenic Mycobacterium tuberculosis (Mtb). Tools that can track the replication status of viable Mtb cells within macrophages are vital for the elucidation of host-pathogen interactions. Here, we present a cephalosphorinase-dependent green trehalose (CDG-Tre) fluorogenic probe that enables fluorescence labeling of single live Bacille Calmette-Guérin (BCG) cells within macrophages at concentrations as low as 2 μM. CDG-Tre fluoresces upon activation by BlaC, the β-lactamase uniquely expressed by Mtb, and the fluorescent product is subsequently incorporated within the bacterial cell wall via trehalose metabolic pathway. CDG-Tre showed high selectivity for mycobacteria over other clinically prevalent species in the Corynebacterineae suborder. The unique labeling strategy of BCG by CDG-Tre provides a versatile tool for tracking Mtb in both pre- and postphagocytosis and elucidating fundamental physiological and pathological processes related to the mycomembrane.

Citation

Tingting Dai, Jinghang Xie, Qihua Zhu, Mireille Kamariza, Ke Jiang, Carolyn R Bertozzi, Jianghong Rao. A Fluorogenic Trehalose Probe for Tracking Phagocytosed Mycobacterium tuberculosis. Journal of the American Chemical Society. 2020 Sep 09;142(36):15259-15264