id0c00025_si_001.pdf (124.8 kB)
Advancement of GyrB Inhibitors for Treatment of Infections Caused by Mycobacterium tuberculosis and Non-tuberculous Mycobacteria
journal contribution
posted on 2020-03-25, 17:34 authored by Suzanne S. Stokes, Rajender Vemula, Michael J. PucciThe
prospect of ever increasing antibiotic resistance eroding currently
available treatment options for bacterial infections underscores the
need to continue to identify new antibiotics, preferably those that
act on novel targets or with novel mechanisms of action. Bacterial
gyrase B subunit (GyrB), an essential component of bacterial gyrase
required for successful DNA replication, represents such a target.
We describe recent examples of GyrB inhibitors and point out their
potential utility for treatment of mycobacterial diseases caused by Mycobacterium tuberculosis (TB) and non-tuberculous mycobacteria
(NTM). Current therapeutic options for these diseases are often suboptimal
due to resistance to current standard of care antibiotics. A future
GyrB inhibitor-based antibiotic could offer a new and effective addition
to the armamentarium for treatment of mycobacterial diseases and possibly
for infections caused by other bacterial pathogens. One GyrB inhibitor,
SPR720, has recently completed a first-in-human clinical trial and
is in clinical development for the treatment of NTM and TB infections.