TEXAS A&M (US) — By manipulating the way bacteria “talk” to each other, researchers have achieved unprecedented control over the formation and dispersal of biofilms.
Working with E. coli bacteria, researchers employed specific signals sent and received between bacteria to trigger the dispersal of biofilm. The finding is significant because biofilm, a community of bacteria living together, is notoriously difficult to break apart.
A protective and adhesive slime that exhibits increased resistance to outside threats such as antibiotics, biofilm 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, says Thomas Wood, professor of chemical engineering at Texas A&M University.
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. The reactors also benefit from the robust nature of biofilm, a trait that makes the film ideal for use, Wood says.
“We want to eventually make with bacteria all the things we currently make in chemical refineries,” Wood says. “Toward 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 the new research, published in the journal Nature Communications, comes into play.
When cells talk
“Never before has a group discovered proteins that make biofilms disperse and then used them in a synthetic circuit,” Wood says. “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, researchers were 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,” explains Arul Jayaraman, associate professor of chemical engineering. “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 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 that¹s 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 says “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 we¹ve 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.
For example, any ingested drug needs to pass through the microbial consortia that exists inside of a person before acting on its target, Jayaraman explains. Using this model, researchers can now better assess the effect of this consortia on the fate and clearance of the drug molecule.
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