A material made from plastic bottles can knock out a drug-resistant fungal infection that the Centers for Disease Control and Prevention predicts will become a more serious health problem in coming years.
Antibiotic-resistant bacteria and fungi kill at least 23,000 people in the U.S. alone each year, and many of these microbial infections are acquired by people hospitalized for other reasons. Research groups around the world are exploring a variety of ways to address the problem, including hunting for novel kinds of antibiotics (see “Bacteria Battle Generates New Antibiotics”) and creating sutures coated with bacteria-killing viruses (see “Using Viruses to Kill Bacteria”).
Another approach involves using biologically active materials that punch holes in the membranes surrounding each microbial cell. These membrane-attacking compounds mimic one of the body’s natural defenses—antimicrobial peptides that insert themselves into a microbe’s outer membrane and break open the bug. IBM Research has developed such a compound—a small molecule that self-assembles into a polymer-like complex capable of killing Candida albicans fungi infecting the eyes of mice. The work was published today in Nature Communications.
“Usually, it is difficult to make antifungal agents because fungal cells are very similar to human cells,” says Kenichi Kuroda, a materials chemist at the University of Michigan who is also working on antimicrobial materials. The challenge is that many microbe-killing drugs work by sabotaging a molecular process inside the pathogen’s cells. And while the molecular machinery of bacteria is usually sufficiently distinct from human cellular machinery to avoid overlapping effects, fungal cells are much closer.
The new IBM compound has not yet been tested in humans, but the researchers say that in mice with a Candida infection in their eyes, the compound killed the fungus more effectively than a widely used antifungal drug without causing harm. And whereas Candida developed resistance to an existing antifungal drug after six treatments, it did not develop resistance to the new compound even after 11 treatments, the team reports.
That ability to avoid resistance may be thanks to the fact that the compound kills by disrupting the microbes’ outer membrane. Unlike antibiotics, which typically work slower and therefore enable a population of bacteria to evolve resistance to a drug’s function, “these kinds of biomaterials have a quick action,” says Kuroda, whose is also focusing on attacking microbial membranes.
IBM developed the polymer-like material using techniques that are well-established in microelectronics but relatively new to biology, says James Hedrick, the IBM Research materials scientist leading the work. The compound belongs to a branch of materials sometimes referred to as molecular glasses. The compound starts off as many individual small molecules, but in water, these individual molecules coalesce into a larger structure that is similar to a polymer, but with weaker bonds between each molecule. This means that the material degrades over time.
“With time it’s going to fall apart, and going to pass through the body,” Hedrick says. “You want them to do their business and then go away, and you don’t want them to accumulate in the body, in waterways, and in our food.”
The starting material comes from a common plastic known as PET. Hedrick says whenever he needs more starting material, he just goes to the nearest recycling bin in the San Jose-based IBM Research building, finds a plastic bottle, and cuts a piece of out of it.
Working with collaborators in Singapore who handle the animal testing branch of the project, Hedrick says a similar compound can knock out an antibiotic-resistant bacterial infection known as MRSA. By injecting that compound into the tail veins of mice, the researchers have been able to clear a MRSA infection from their blood.
“We can do many things with [these compounds],” says Hedrick. “We can make them into hydrogels to treat MRSA skin infections and they can go into everything from shampoo to mouthwash.”