Clifton E. Barry III, PhD
Tuberculosis Research
Section
National Institute of Allergy &
Infectious Diseases , National
Institutes of Health
Thursday, February 18, 2016
11:00 AM
Chemistry Room #1315
Exploiting the biochemistry of
trehalose to develop real-time imaging
probes for tuberculosis
Mycobacterium tuberculosis is a devastating human
pathogen that is globally responsible for 3 million
deaths per year and infects one-third of the entire
human population. The development of new drugs
and vaccines is complicated by the century-old,
poorly sensitive and poorly specific methods used for
its detection in human lungs. The disaccharide
trehalose plays an integral role in the biology of this
organism, acting as both shuttle and destination for
the very long chain mycolic acids that form the
outermost layers of the outer cell envelope. The
enzymes that trans-esterify mycolic acids on to, and
off of, trehalose are three isoforms of the most
abundant secreted protein in the cell known
collectively as Antigen 85. We probed the selectivity
of these enzymes using a library of trehalose analogs
and identified positions on trehalose that could be
substituted while still maintaining the ability to act
as substrates for Antigen 85. Armed with that
knowledge we synthesized and assayed 18F-trehalose
analogs for use as real-time imaging agents using
Positron
Emission
Tomography-Computed
Tomography (PET-CT) in TB-infected animals and
have shown that these specifically label viable
bacteria. These probes appear highly specific for TB
and their utility for monitoring response to
treatment, vaccine efficacy and risk of progression
to active disease after infection in humans are
currently being explored.