Acute Modulation of Mycobacterial Cell Envelope Biogenesis by Front‐Line Tuberculosis Drugs. Issue 19 (14th April 2018)

• Record Type: Journal Article
• Authors: Rodriguez‐Rivera, Frances P.; Zhou, Xiaoxue; Theriot, Julie A.; Bertozzi, Carolyn R.
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 19(2018)
• Page Start: 5267
• Page End: 5272
• Publication Date: 2018-04-14
• Subjects: cell envelope -- drug discovery -- live-cell imaging -- metabolic labeling -- mycobacteria; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201712020
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Front‐line tuberculosis (TB) drugs have been characterized extensively in vitro and in vivo with respect to gene expression and cell viability. However, little work has been devoted to understanding their effects on the physiology of the cell envelope, one of the main targets of this clinical regimen. Herein, we use metabolic labeling methods to visualize the effects of TB drugs on cell envelope dynamics in mycobacterial species. We developed a new fluorophore–trehalose conjugate to visualize trehalose monomycolates of the mycomembrane using super‐resolution microscopy. We also probed the relationship between mycomembrane and peptidoglycan dynamics using a dual metabolic labeling strategy. Finally, we found that metabolic labeling of both cell envelope structures reports on drug effects on cell physiology in two hours, far faster than a genetic sensor of cell envelope stress. Our work provides insight into acute drug effects on cell envelope biogenesis in live mycobacteria. Abstract : TB or not TB? A new fluorophore–trehalose conjugate was developed to image trehalose monomycolates of the mycomembrane (MM). MM and peptidoglycan (PG) dynamics were simultaneously probed using a dual metabolic labeling strategy. The results showed that front‐line TB drugs produce acute changes in cell envelope biogenesis.