Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 142, Issue 36, Pages 15259-15264Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.0c07700
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Funding
- NIAID [R01AI125286, R37AI051622]
- Center for Molecular Analysis and Design (CMAD) at Stanford
- NIH [NS069375]
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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-Guerin (BCG) cells within macrophages at concentrations as low as 2 mu M. CDG-Tre fluoresces upon activation by BlaC, the beta-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.
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