By manipulating the way bacteria “talk” to each
other, researchers at Texas A&M University have achieved an unprecedented
degree of control over the formation and dispersal of biofilms—a finding with
potentially significant health and industrial applications, particularly to
bioreactor technology.
Working
with E. coli bacteria, Professor Thomas K. Wood and Associate Professor
Arul Jayaraman of the university’s Artie McFerrin Department of Chemical
Engineering have employed specific signals sent and received between bacteria
to trigger the dispersal of biofilm. Their findings appear online in Nature
Communications.
The
finding is a significant one, Wood said, because biofilms are notoriously
difficult to break apart. A community of bacteria living together, a biofilm is
a protective and adhesive slime that exhibits increased resistance to outside
threats such as antibiotics. The film can grow on a variety of living and
nonliving surfaces, including submerged rocks, food, teeth (as plaque), and
biomedical implants such as knee and hip replacements.
While
biofilm can pose serious health risks, its use in industrial applications such
as in bioreactors is offering hope for an alternative-fuels future, Wood said.
Genetically tweaked and grown in these reactors, biofilm can be used to produce
a variety of chemicals such as propanol and butanol. And because the bacteria
within biofilm feed on glucose, bioreactors using biofilms have the potential
to help transform the economy. These reactors also benefit from the robust
nature of biofilm, a trait that makes the film ideal for use, Wood said.
“We
want to eventually make with bacteria all the things we currently make in
chemical refineries,” Wood said. “Towards this goal, the reactor of
the future is a biofilm reactor. The main reason is if someone who is operating
the reactor, for example, coughs, it doesn’t go crazy. If the pH level drops,
the biofilm will remain robust and the cells won’t die whereas if cells were
growing independently (not in a biofilm), and there was a change inside the
reactor, you could lose all the cells and the products they are
producing.”
But
before this technology can be realistically implemented, scientists and
engineers need to be able to control a number of variables associated with the
film, such as how much of the film grows in the reactor, how long it must
remain in the reactor and in what proportions different biofilms coexist within
the reactor.
That’s
where Wood and Jayaraman’s research comes into play.
“Never
before has a group discovered proteins that make biofilms disperse and then
used them in a synthetic circuit,” Wood said. “We took advantage of
the fact that cells talk to each other. We took another bacterium’s signal and
had E. coli make it because it doesn’t normally make it. We also
inserted the receiving mechanism in E. coli. And we were responsible for
putting an ‘on-off switch’ within the bacteria because we wanted this signal
broadcast continuously.”
By
genetically inserting a foreign chemical signal from another bacterium—Pseudomonas aeruginosa—into E. coli,
the research team was able to force one group of E. coli to continuously
emit this chemical signal. The group then inserted this group of bacteria into
an environment where a biofilm was present. That existing biofilm was also
genetically modified to receive the chemical signal. Once the signal was
received, Wood explains, the bacteria within the biofilm responded by breaking
apart and leaving the environment, effectively dispersing the biofilm.
“We
developed novel miniature models of biofilm reactors where we can exquisitely
control which bacterial species is colonizing, for what duration, and to which
signals it is exposed to during growth,” Jayaraman explained. “Apart
from enabling us to control the reactors, this also allows us to investigate
several experimental conditions in a high-throughput manner, which is essential
for optimizing bioprocesses.”
This
unprecedented degree of control over biofilm, Wood said, is key to advancing
bioreactor technology because it enables scientists to work with bacteria,
growing them at greater densities and in specific proportions. For example, by
controlling the formation and dispersal of biofilms, scientists would be able
to switch the production of a bioreactor from one chemical to another with
limited downtime, in effect creating a seamless manufacturing refinery that
continuously pumps out in-demand chemicals. And that’s exactly where the team’s
research is leading.
“In
the next application, we want to maintain a consortia—a mix of different
bacteria—where one group makes the first part of some important chemical and
the other group makes the second part that is needed,” Wood said.
“Also, both groups could make two things that are needed at the same time
and you don’t want to separate. We want to create complex groupings of bacteria
to create complex chemicals. To do this, the bacteria groups need to be in the
right proportions, and no one had yet approached this. This can be done now
with what we’ve discovered.”
What’s
more is that these technologies are also applicable to drug discovery, drug
delivery, and pharmaceutical applications, as they can be used to mimic the
human body environment, Jayaraman noted. For example, any ingested drug needs
to pass through the microbial consortia that exists inside of a person before
acting on its target, he explained. Using this model, researchers can now
better assess the effect of this consortia on the fate and clearance of the
drug molecule, he said.
SOURCE – Texas A&M University