Chemical Mycobateriology

Tuberculosis (TB) is a chronic pulmonary disease caused by Mycobacterium tuberculosis (Mtb), which
infects approximately one quarter of the world’s population. A variety of drugs have been identified that
rapidly kill Mtb and its relatives in vitro, yet clinical treatment requires at least 6 months of combination
therapy and resistance is rampant. Furthermore, the current state-of-the-art for detection of Mtb infection
employs cumbersome methods that were developed more than 80 years ago. Herein we propose to
develop new methods for detection of Mtb that can be employed in low resource settings, and to develop
new screens for potential TB drugs, as well as to perform fundamental studies on the role of mycobacterial
lipids in virulence.
In this renewal application of R37 AI051622 entitled “Chemical Mycobacteriology”, we propose the
following four Aims: (1) to develop probes based on the fluorogenic Nile Red and 3-hydroxychromone dyes,
which can be used to detect Mtb with low-power, low-cost microscopes; (2) to establish a magnetic bead-
based enrichment platform that can be deployed at the point-of-care to enhance detection of fluorescently
labeled Mtb cells; (3) to deploy metabolic labeling as a readout for high-throughput drug screens to
decrease time and expense in discovery of new TB drugs; and (4) to employ bioorthogonal labeling and
chemical biology approaches to elucidate the role of phthiocerol dimycocerosates (PDIM) lipids in
mycobacterial virulence.

Grant Number: 5R37AI051622-24
NIH Institute/Center: NIH
Principal Investigator: Carolyn Bertozzi