Acute Modulation of Mycobacterial Cell Envelope Biogenesis by Front-Line Tuberculosis Drugs

Frances P. Rodriguez-Rivera, Xiaoxue Zhou, Julie A. Theriot, Carolyn R. Bertozzi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)5267-5272
Number of pages6
JournalAngewandte Chemie - International Edition
Volume57
Issue number19
DOIs
StatePublished - May 4 2018

Keywords

  • cell envelope
  • drug discovery
  • live-cell imaging
  • metabolic labeling
  • mycobacteria

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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