Col. John “Hannibal” Smith, the cigar-chomping leader of the iconic 1980s TV squad, “The A-Team,” had a famous saying: “I love it when a plan comes together.” The same might be said by bacteria – were they to speak English – regarding how they make humans sick.
Bacteria communicate with one another using small signal molecules and, sometimes change their behavior as a result. This process, known as quorum sensing, is used by some bacteria to “turn-on” an active infection lifestyle and pose a serious risk to human health.
A grant recently awarded to Florida Tech is looking at how to cut the lines of communication used in the bacteria’s sickness-inducing plan.
The grant, titled “Combating Pseudomonas Virulence with Cyclodextrin-Based Artificial Enzymes,” looks to silence that bacterial communication by deploying a lampshade-shaped molecule called a cyclodextrin to sequester or trap the signal molecules. Using an email analogy, the cyclodextrin molecules essentially filter the messages to a folder where they likely wouldn’t be seen by their intended recipient. The grant comes as part of a larger research effort involving biomedical and chemical engineering sciences Ph.D. candidate Eric Ziegler, biomedical and chemical engineering sciences/ocean engineering and marine sciences associate professor Andrew Palmer, and biomedical and chemical engineering sciences associate professor Alan Brown.
While the team acknowledges that deploying a large number of cyclodextrins could disable bacterial communication just by sequestering the large amount of messaging molecules, a key aspect of the grant focuses on deploying only a few cyclodextrins that not only can sequester the signal molecules but also inactivate them. To do that, the team is looking to modify the cyclodextrins and change certain properties to facilitate better performance.
“We pick a molecular property we are interested in pursuing and we see how molecular structure influences that property,” Brown said. “For this project, basically I know about the organic chemistry that goes into the molecule-making and I also know about the spectroscopic techniques used to characterize things.”
To date, the collaboration has shown where the bacteria’s communication system is stable and can be studied effectively. The researchers also looked at how the signal molecules and their inactivated forms behave with respect to being trapped by cyclodextrin.
The research being pursued might have a therapeutic role in bacterial infections, especially as bacteria develop increasing resistance to antibiotics.
“What we’re trying to do is: instead of applying a lethal amount of pressure, like what antibiotics do in killing bacteria, we are trying to target what makes (the bacteria) harmful, which won’t kill them, but will prevent them from adversely affecting people. It would be used sort of as a therapeutic, which could be used in combination with antibiotic therapy,” Ziegler said.
As bacteria research has advanced from being in a Petri dish or test tube, there still is progress to be made. The team is using C. elegans roundworms as a host for the tests, which they hope will allow them to better understand how this defense may perform in a host environment.
“Once you get the testing out in a larger environment, it’s more complicated,” Palmer said. “How do you stop the conversation at the party?”