2050, antibiotic-resistant bacterial infections will kill 10 million
people per year, if no new drugs are developed, estimated the United Kingdom commission on antimicrobial resistance.
Over the past few decades, many bacteria have become resistant to
existing antibiotics, and few new drugs have emerged. To help rebuild the arsenal against infectious diseases, many
scientists are turning toward naturally occurring proteins known as
antimicrobial peptides, which can kill not only bacteria but other
microbes such as viruses and fungi.
‘An antimicrobial peptide that can destroy many types of bacteria, including some that are resistant to most antibiotics, has been developed by researchers.’
A team of researchers at MIT, the
University of Brasilia, and the University of British Columbia has now
engineered an antimicrobial peptide that can destroy many types of
bacteria, including some that are resistant to most antibiotics.
"One of our main goals is to provide solutions to try to combat
antibiotic resistance," says MIT postdoc Cesar de la Fuente. "This
peptide is exciting in the sense that it provides a new alternative for
treating these infections, which are predicted to kill more people
annually than any other cause of death in our society, including
De la Fuente is the corresponding author of the new study, and one
of its lead authors along with Osmar Silva, a postdoc at the University
of Brasilia, and Evan Haney, a postdoc at the University of British
Columbia. Timothy Lu, an MIT associate professor of electrical
engineering and computer science, and of biological engineering, is also
an author of the paper, which appears in the Scientific Reports
Improving on nature
Antimicrobial peptides, produced by all living organisms as part of
their immune defenses, kill microbes in several different ways. First,
they poke holes in the invaders' cell membranes. Once inside, they can
disrupt several cellular targets, including DNA, RNA, and proteins.
These peptides also have another critical ability that sets them
apart from traditional antibiotics: They can recruit the host's immune
system, summoning cells called leukocytes that secrete chemicals that
help kill the invading microbes.
Scientists have been working for several years to try to adapt these
peptides as alternatives to antibiotics, as bacteria become resistant
to existing drugs. Naturally occurring peptides can be composed of 20
different amino acids, so there is a great deal of possible variation in
"You can tailor their sequences in such a way that you can tune them
for specific functions," de la Fuente says. "We have the computational
power to try to generate therapeutics that can make it to the clinic and
have an impact on society."
In this study, the researchers began with a naturally occurring
antimicrobial peptide called clavanin-A, which was originally isolated
from a marine animal known as a tunicate. The original form of the
peptide kills many types of bacteria, but the researchers decided to try
to engineer it to make it even more effective.
Antimicrobial peptides have a positively charged region that allows
them to poke through bacterial cell membranes, and a hydrophobic stretch
that enables interaction with and translocation into membranes. The
researchers decided to add a sequence of five amino acids that would
make the peptides even more hydrophobic, in hopes that it would improve
their killing ability.
This new peptide, which they called clavanin-MO, was very potent
against many bacterial strains. In tests in mice, the researchers found
that it could kill strains of Escherichia coli and Staphylococcus aureus
that are resistant to most antibiotics.
Another key advantage of these peptides is that while they recruit
immune cells to combat the infection, they also suppress the overactive
inflammatory response that can cause sepsis, a life threatening
"In this single molecule, you have a synthetic peptide that can kill
microbes - both susceptible and drug-resistant - and at the same time
can act as an anti-inflammatory mediator and enhance protective
immunity," de la Fuente says.
The researchers also found that these peptides can destroy certain
biofilms, which are thin layers of bacterial cells that form on
surfaces. That raises the possibility of using them to treat infections
caused by biofilms, such as the Pseudomonas aeruginosa infections that
often affect the lungs of cystic fibrosis patients. Or, they could be
embedded into surfaces such as tabletops to make them resistant to
Other possible applications for these peptides include antimicrobial
coatings for catheters, or ointments that could be used to treat skin
infections caused by Staphylococcus aureus or other bacteria.
If these peptides are developed for therapeutic use, the researchers
anticipate that they could be used either in stand-alone therapy or
together with traditional antibiotics, which would make it more
difficult for bacteria to evolve drug resistance. The researchers are
now investigating what makes the engineered peptides more effective than
the naturally occurring ones, with hopes of making them even better.