New TB drug candidates developed from soil bacteria
A new treatment for tuberculosis (TB) is set to be developed using compounds derived from bacteria that live in soil -- according an international collaboration of researchers, including the University of Warwick.
The research partnership -- involving the University of Warwick,
and spanning institutions from Australia, Canada and the USA --
has discovered a compound which could translate into a new drug
lead for TB.
The group looked at soil bacteria
compounds, known to effectively prevent other bacteria growing
around them. Using synthetic chemistry, the researchers were
able to recreate these compounds with structural variations,
turning them into more potent chemical analogues.
When
tested in a containment laboratory, these analogues proved to be
effective killers of Mycobacterium tuberculosis -- the bacterium
which causes TB.
These chemicals target an enzyme in
Mycobacterium tuberculosis called MraY, which catalyses a
crucial step in building the cell wall around a bacterium.
Attacking this part -- a potential 'Achilles' heel' of the
bacterium -- provided an essential pathway for the antibacterial
compounds to attack and destroy TB strains.
Key
reagents and expertise in antimicrobial resistance from the
research groups of Dr David Roper, Professor Chris Dowson and
Professor Tim Bugg at the University of Warwick, played a
crucial role in successfully targeting TB bacteria with the new
compounds.
Believed by many to be a relic of past
centuries, TB still causes more deaths than any other infectious
disease, including HIV/AIDs.
In 2015 there were an
estimated 10.4 million new cases of TB and 1.4 million deaths
from the disease.
Mycobacterium tuberculosis is
becoming increasingly resistant to current therapies, meaning
there is an urgent need to develop new and effective TB
drugs.
In 2015 an estimated 480,000 cases were
unresponsive to the two major drugs used to treat TB. It is
estimated more than 250,000 TB deaths were from drug-resistant
infections.
Dr David Roper, from the University of
Warwick's School of Life Sciences, comments:
"The
University of Warwick is a central hub in the UK for
antimicrobial resistance research and we have crucial expertise
in the bacterial cell wall as a target for new antibiotics.
"This
study highlights the international nature of our research and
how such collaboration can bring new innovation in drug
discovery and biomedicine."
The research,
'Sansanmycin Natural Product Analogues as Potent and
Selective Anti-Mycobacterials that Inhibit Lipid I
Biosynthesis'
is published in Nature Communications.
Journal Reference:
- Anh T. Tran, Emma E. Watson, Venugopal Pujari, Trent Conroy, Luke J. Dowman, Andrew M. Giltrap, Angel Pang, Weng Ruh Wong, Roger G. Linington, Sebabrata Mahapatra, Jessica Saunders, Susan A. Charman, Nicholas P. West, Timothy D. H. Bugg, Julie Tod, Christopher G. Dowson, David I. Roper, Dean C. Crick, Warwick J. Britton, Richard J. Payne. Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis. Nature Communications, 2017; 8: 14414 DOI: 10.1038/ncomms14414
Source:
University of Warwick
