New research at the A. James
Clark School of Engineering could prevent bacterial infections using tiny
biochemical machines--nanofactories--that can confuse bacteria and stop them
from spreading, without the use of antibiotics.
A paper about the research is featured in the current issue of Nature Nanotechnology.
"Engineered biological nanofactories trigger quorum sensing response in
targeted bacteria," was authored by Clark School alumnus Rohan Fernandes
(Ph.D. '08, bioengineering), graduate student Varnika Roy (molecular and cell
biology), graduate student Hsuan-Chen Wu (bioengineering), and their advisor,
William Bentley (professor and chair, Fischell Department of Bioengineering).
The group's work is an update on their original nanofactories, first developed
in 2007. Those nanofactories made use of tiny magnetic bits to guide them to
the infection site.
"This is a completely new, all-biological version," he says. "The
new nanofactories are self-guided and targeted. We've demonstrated for the first
time that they're capable of finding a specific kind of bacterium and inducing
it to communicate, a much finer level of automation and control."
The new nanofactories can tell the difference between bad (pathogenic) and good
bacteria. For instance, our digestive tracts contain a certain level of good
bacteria to help us digest food. The new nanofactories could target just the
bad bacteria, without disrupting the levels of good bacteria in the digestive
tract (a common side effect of many antibiotics). Nanofactories target the bacteria
directly rather than traveling throughout the body, another advantage over traditional
Bacterial cells talk to each other in a form of cell-to-cell communication known
as quorum sensing. When the cells sense that they have reached a certain quantity,
an infection could be triggered. The biological nanofactories developed at the
Clark School can interrupt this communication, disrupting the actions of the
cells and shutting down an infection.
Alternatively, the nanofactories could trick the bacteria into sensing a quorum
too early. Doing so would trigger the bacteria to try to form an infection before
there are enough bacterial cells to do harm. This would prompt a natural immune
system response capable of stopping them without the use of drugs.
Because nanofactories are designed to affect communication instead of trying
to kill the bacteria, they could help treat illness in cases where a strain
of bacteria has become resistant to antibiotics.
"The work by Dr. Bentley is extremely exciting as he is using the ability
of engineering to 'build' using nature based components," says Philip Leduc,
associate professor in the Departments of Mechanical and Biomedical Engineering
and the Lane Center for Computational Biology and Biological Sciences at Carnegie
Mellon University. "Understanding the science of cells is wonderful, but
then using these components and constructing systems that leverage biological
advantages is a huge step forward. His work in this paper uses his synthetic
biology approach to build new nanofactories toward new areas of antimicrobials
as well as opening new findings in quorum sensing."
The nanofactories' ability to alter cell-to-cell communication isn't limited
to fighting infections.
"Quorum sensing and signaling molecules are actually used to accomplish
a lot of things," Bentley explains. "Sometimes disease develops because
communication is not taking place--a good example is digestive disorders that
involve an imbalance of bacteria in the digestive tract. In that case, nanofactories
could be used to start or increase communication instead of disrupting it."