We call them “superbugs”—and antibiotic-resistant bacteria are literally an evolving threat. Doomsday prophets and other pessimists foresee a future where superbugs run amok, overwhelming doctors’ efforts to rid once easily treatable bacterial infections. Even optimists recognize the problem of antibiotic resistance as a serious public health threat. That’s why researchers around the world are looking for novel approaches to control bacterial infections, and one promising approach is taking shape in labs at UW-Madison.
Collaborators David Lynn, the Duane H. and Dorothy M. Bluemke professor and Vilas Distinguished Achievement professor in chemical and biological engineering at UW-Madison, and Helen Blackwell, a professor of chemistry at UW-Madison, approach the control of bacterial infections not by blasting them with toxic antibiotics, but instead by inhibiting the ability of bacteria to become infectious in the first place.
Many common species of bacteria, including those that cause dangerous infections, are actually fairly harmless at certain stages in their lifecycle. These bacteria become infectious—or virulent—only when they sense that their numbers have crossed a certain threshold. Once that threshold is crossed, a message travels through the colony, which signals that it’s time to go on the offense and infect their host. This communication process is called quorum sensing, and it’s a potential weak spot for bacteria.
That’s because researchers are beginning to understand the mechanisms behind quorum sensing so well that they’ve been able to produce molecules that inhibit the process. It’s a potential breakthrough not only in preventing new infections, but also in potentially slowing the pace of antibiotic resistance. Quorum sensing inhibitors don’t kill bacteria—they simply render them impotent, allowing a host’s immune system to zap them before they become infectious.
Antibiotic resistance is the product of the selective pressure of toxic drugs that kill most bacteria, leaving behind only those with resistant traits—however, quorum sensing inhibitors don’t kill bacteria and therefore should not create the selective pressure that leads to antibiotic resistance. Blackwell’s lab has successfully produced many different types of quorum sensing inhibitor molecules.
Meanwhile, Lynn’s lab is developing novel methods for delivering these quorum sensing inhibitors to the body. New research published in the journal ACS Infectious Diseases describes their latest approach, using a technique called electrospinning that produces tiny nanofibers that contain the inhibitor molecules. “The technique involves passing a polymer solution through a needle,” says Lynn. “That needle has a large electrical potential, resulting in basically a jet of wildly fluctuating polymer solution from the tip of that needle. The dimensions of that jet just happen to be on the nanoscale.”
The solvent then evaporates and leaves behind fibers with diameters on the order of several hundred nanometers. These fibers, which contain the inhibitor molecules can be collected as non-woven ‘mats’ or coatings on the surfaces of many kinds of materials, including common mesh-like wound dressings.
Perhaps what makes the nanofiber delivery method most exciting is that the nanofibers control the release of the inhibitor molecules as they degrade.
This timed release is a key goal of Lynn’s research as quorum sensing inhibitors aren’t much use if they don’t stick around long. The nanofibers in this current research have controlled release of the inhibitor for about two weeks, but some of Lynn’s other approaches have controlled release up to eight months.
In addition to wound dressing applications, Lynn sees potential for the approach to be used in medical implant devices and both on its own or in concert with conventional antibiotics. He continues to work on other quorum sensing inhibitor delivery methods, and he and Blackwell are teaming up with researchers in the veterinary medicine and microbiology programs at UW-Madison to begin testing in mouse models.
Still, Lynn cautions that it will be some time before quorum sensing inhibitors are part of doctors’ antibacterial armament. “This anti-virulence approach is brand new and there’s a lot of science that still needs to be understood,” Lynn says. “There’s a lot of work to do yet.”
Author: Will Cushman