t’s a battle that seems ripped from a sci-fi film: Scientists are racing to develop new weapons to destroy the slimy colonies of bacteria, known as biofilms, that cause tens of thousands of deaths across the US each year.
Biofilms are the leading cause of infections acquired in hospitals. They grow on medical devices such as heart valves, pacemakers, and catheters. They take root inside wounds, pulsing and rippling as they spread. Some even sprout tiny legs — and use them to walk across surfaces.
Encased in gooey protective sheaths, biofilms are exceptionally hard to stop. Many are impervious to antibiotics. They also cost the health care system billions each year, as patients often require surgery to remove and replace contaminated implants.
So researchers and biotech startups are testing new methods of attack, from coating medical devices with spiky coverings to blasting bacteria with electrical fields to interrupting the chemicals that cells inside biofilm colonies use to send messages to each other. Just this week, researchers at Ohio State announced they’d invented a way to coat the surfaces of medical devices (and shampoo bottles) with Y-shaped nanoparticles of quartz in a bid to block biofilms from latching on tight.
“The variety of things being tried is just amazing,” said Karin Sauer, a professor of biology at Binghamton University in New York who has been studying biofilms for 16 years. “People have to be extremely creative because biofilms are so difficult to eradicate.”
Here’s a look at the battle:
What are biofilms?
Unlike free-floating bacteria that drift in fluids, biofilms consist of bacteria that settle onto surfaces and begin to aggregate into large clumps surrounded by a protective coating of DNA, proteins, and polysaccharides — slime to you and me.
Biofilms are different from so-called superbugs, like MRSA, that have evolved a resistance to antibiotics. Each individual bacteria in a biofilm would, on its own, be susceptible to modern drugs. But when they clump together, the bacteria morph into complex 3-D structures.
Using a vocabulary of chemicals, the bacteria in the biofilms self-organize and divide up tasks, some growing and secreting slime, some dispersing to colonize new areas, and some hibernating until they are needed. The biofilm structures even contain channels to take in nutrients and expel waste.
“They communicate with each other and coordinate their activity,” Sauer said. “In a biofilm, you see cooperative behavior. It’s a lifestyle choice.”
Is this a new menace?
Not at all.
Way back in 1684, Dutch scientist Antonie van Leeuwenhoek found biofilms in his own dental plaque (which he called “scurf”). He noted they were more difficult to kill than solitary bacteria.
The term “biofilm” was first used in publication in 1975, according to Montana State University’s Center for Biofilm Engineering.
In more recent years, the impact of biofilms on human health has become apparent: Their tolerance to antibiotics is at least twice — and perhaps as much as 1,000 times — stronger than normal bacteria, according to Sauer. They cause deadly infections, often in patients already weakened by surgery or diabetes, and cost the health care system billions each year.
As a result, interest in and funding for biofilm research has exploded. The National Institutes of Health funded more than 500 grants mentioning the word biofilm in the last year alone.
Why are biofilms so hard to kill?
Let us count the ways.
First there’s the slime, which antibiotics and chemicals have difficulty penetrating. In addition, electrical charges on the slime’s surface can form a barrier that keeps out antibiotics.
Because many cells deep within a biofilm are nutrient- and oxygen-starved, they grow fairly slowly — and are therefore less susceptible to antibiotics, which work best on actively dividing cells. To make matters worse, biofilms contain zombie-like “persister” cells which lie dormant when antibiotics are present but spring into action after antibiotic treatment ends.
Finally, cells within biofilms can organize themselves to pump drugs right out of cells — something Sauer called “a kind of bulimic behavior.”
So, what’s being done?
Academic labs and biotech startups are bubbling over with ideas.
One tactic: Cover surgical implants — and perhaps wounds — with a coating that can ward off biofilms, even just for a few days, so healing can begin. Silver is one potential coating; it’s extremely toxic to bacteria. Researchers are also working on synthetic coatings that can release drugs and enzymes designed to gobble up proteins and perhaps stop biofilms in their tracks.
Another approach: Wrap implants with materials so bumpy that biofilms can’t find a way in. Colorado-based Sharklet Technologies makes biofilm-repelling materials for wounds and catheters inspired by the rough diamond-shaped patterns in sharkskin. Other labs are fabricating surfaces studded with tiny pillars, modeled after the bacteria-repelling spikes found on the wings of cicadas and dragonflies.
Zapping the biofilms could help as well: Exposing the slimy clumps to electrical fields can make them more permeable to drugs and can disrupt their ability to cling to surfaces. Arizona-based Vomaris Innovations markets a wound dressing called Procellera that generates microcurrents to aid in wound healing.
Then there’s the yank-it-out approach: Ohio-based startup ProclaRx is developing a treatment containing antibodies that attach to proteins within a biofilm and pull them out, the company says, “much like removing a rivet.”
Biofilms depend on communication to form, cooperate, and survive; Princeton molecular biologist Bonnie Bassler calls it “bacterial Esperanto.” Microbiologists are trying to eavesdrop on this chemical language, known as “quorum sensing,” and use it against the bacterial menace. Work is underway to block both the senders and receivers of signals and the messages themselves.
Other labs are screening tens of thousands of natural compounds in a search for anti-biofilm agents. Last month, researchers at the University of Florida announced the discovery of a compound called darwinolide, derived from a spiky Antarctic sponge, that killed 98 percent of cells in a biofilm.
And there’s a lot of basic research going on, too, to understand biofilms in all their beautiful and horrifying complexity.
“How do they form? How do they make their structures?” Sauer asked. “Can we use some of this knowledge to stop them?”