A new
group of antibiotics with a unique approach to attacking bacteria has been
discovered, making it a promising clinical candidate in the fight against
antimicrobial resistance.
The
newly-found corbomycin and the lesser-known complestatin have a
never-before-seen way to kill bacteria, which is achieved by blocking the
function of the bacterial cell wall. The discovery comes from a family of
antibiotics called glycopeptides that are produced by soil bacteria.
The
researchers also demonstrated in mice that these new antibiotics can block
infections caused by the drug resistant Staphylococcus aureus which is a group
of bacteria that can cause many serious infections.
The
findings were published in Nature today.
"Bacteria have a wall around the outside of their cells that gives them shape
and is a source of strength," said study first author Beth Culp, a PhD candidate
in biochemistry and biomedical sciences at McMaster.
"Antibiotics like penicillin kill bacteria by preventing building of the wall,
but the antibiotics that we found actually work by doing the opposite -- they
prevent the wall from being broken down. This is critical for cell to divide.
"In
order for a cell to grow, it has to divide and expand. If you completely block
the breakdown of the wall, it is like it is trapped in a prison, and can't
expand or grow."
Looking at the family tree of known members of the glycopeptides, researchers
studied the genes of those lacking known resistance mechanisms, with the idea
they might be an antibiotic demonstrating a different way to attack bacteria.
"We
hypothesized that if the genes that made these antibiotics were different, maybe
the way they killed the bacteria was also different," said Culp.
The
group confirmed that the bacterial wall was the site of action of these new
antibiotics using cell imaging techniques in collaboration with Yves Brun and
his team from the Université de Montréal.
Culp
said: "This approach can be applied to other antibiotics and help us discover
new ones with different mechanisms of action. We found one completely new
antibiotic in this study, but since then, we've found a few others in the same
family that have this same new mechanism."
The
team is led by professor Gerry Wright of the David Braley Centre for Antibiotic
Discovery within the Michael G. DeGroote Institute for Infectious Disease
Research at McMaster.
The
research was funded by the Canadian Institutes of Health Research and the
Ontario Research Fund.
Via Science Daily