You get up in the morning, make coffee, shower, brush your teeth and probably never think about biofilms.
Maybe the school nurse calls because your child has an earache. You take her to the doctor’s office, where you’re next in line behind the person with the sinus infection. The climate-controlled office means no windows are open, so you aren’t bothered by the noise of the water main repair going on outside. And still, biofilms are the furthest thing from your mind.
Yet, biofilms were in your faucet, your coffee maker and the shower (don’t forget the curtain!). It was what you brushed off your teeth, and it’s likely the cause of the earache and the sinusitis. It’s in the air vent and could be the cause of that broken water pipe.
It’s enough to scare you to death — but more about that later.
What is a biofilm? It’s fun to call it slime, but that’s dismissive of the remarkable powers of communication, organization and protection exhibited by single-cell bacteria when they get the message to undergo changes and come together in a kind of microbial flash mob and form a biofilm. And being in a biofilm increases by 1,000-fold the bacteria’s ability to withstand antibiotics.
When not growing in a biofilm, bacteria live as individual, free-floating cells. They can keep us healthy (yogurt requires them) and make us sick (a common cause of food poisoning). When they are free floating, they are easy to treat with antibiotics and antimicrobial agents.
“Once bacteria make contact with a surface — it could be your contact lens, your prosthetic device, your wound — they start forming a biofilm,” says Professor Karin Sauer.
If the result is an infection, it’s hard to treat. Biofilms aren’t impervious to antibiotics, but the amount of antibiotics necessary to kill the bacteria present in the biofilms would likely be toxic to the person being treated. One solution is to disperse the bacteria out of their protective biofilm. Once they are again free floating, they can be eliminated with a reasonable course of antibiotics.
If only it were that simple.
In the state-of-the-art lab in the Biotechnology Building, it’s the biologists vs. the biofilms: Professor Sauer, Associate Professor David Davies, assistant professors Jeffrey Schertzer and Cláudia N. H. Marques, and 18,000 samples of Pseudomonas aeruginosa, the bacterium of choice for most of their research.
The scientists believe that the stability and invulnerability of biofilms hold the key to someday treating chronic diseases and conditions as disparate as sinusitis, Crohn’s and atherosclerosis.
“Chronic disease in human beings is one of the last untapped areas for control,” Davies says. “We get old, we get feeble, and we start to fall to pieces before we die. A lot of that is due to biofilm infections. We can do a great deal to enhance the health of people by tackling these chronic diseases, the ones that don’t kill you right away.”
“The key in all these chronic and recurring diseases is that you never eradicate the biofilm responsible for the infection,” Schertzer says. “You put enough drugs in there that you lose some of the acute symptoms and you think that sinus infection is gone but it’s not, and once antibiotic treatment has stopped, biofilms will grow back.”
Scientists have been growing microorganisms in petri dishes and liquid cultures for more than a century, but it wasn’t until the late 1990s that biologists started to ask questions about how bacteria live in their world — and a biofilm is a community.
There are distinct stages in building a P. aeruginosa biofilm: First, the bacteria begin to attach to a wet surface. Microcolonies form and are then encased in a matrix (slime!) that protects them. Eventually, some bacteria leave the biofilm to start new communities elsewhere — and that’s when they are once again susceptible to antimicrobial agents. All of this can happen because bacteria can easily change which genes they express, thereby altering their behavior, metabolism and even the way in which they interact with the environment. Catching them at the right time is critical to effective antimicrobial treatment.
Knowing this, the Binghamton team sees a variety of opportunities for halting or reversing the formation of biofilms.
Schertzer studies how bacteria communicate by using signaling molecules (similar to how our bodies use hormones). It’s a relatively new area because the idea of bacteria “talking” to each other has been accepted for only about 20 years.
“We know signaling is important in the transition to biofilm,” he says. Key to the process are outer membrane vesicles, which are small spheres on the surface of the cell. “They [the cells] basically produce these small spheres and put things in them. They can put toxins in if they want to use one like a hand grenade to blow up the enemy, or they can put a signal in to send it to a friend if they want to tell him to turn on certain genes.”
Marques wants to know what triggers the bacteria to undergo genetic changes necessary for the biofilm to form within a host. “How do the bacteria recognize the host and change their genetic profile? How does the host react to the bacteria in the biofilm?” she asks.
Sauer has a broad interest in the developmental aspects of biofilms, but she and Davies are focusing, in particular, on how and why biofilms disperse.
“What are the triggers, or signals, that induce the dispersion of biofilms, and how do biofilms perceive those signals?” Sauer asks. “Do they respond to sugars? Nitric oxide? Hydrogen peroxide?”
And when a biofilm is forced to disperse, what are the consequences to the host?
“You might have a biofilm infection for 40 years and do fine; it doesn’t bother you much and it doesn’t kill you,” Davies says. “However, if the biofilms are disrupted, we have a better capability of killing the bacteria. But those bacteria might become more virulent and kill you if we don’t kill them first. So we don’t know if it’s better to disrupt the biofilm or not. We might swamp the immune system.”
Collectively, the team’s goal is to control the formation, dispersion and antimicrobial tolerance of biofilms. In the past year, Davies has patented a biofilm dispersion technology.
“We want to learn everything we can about how biofilms are made, put together and come apart,” Schertzer says.
Understanding biofilms is one hurdle; the other is convincing the medical community that biofilms cause as many diseases as the researchers think they do. If a doctor suspects a bacterial infection, he cultures a sample of blood or fluid. It’s easy proof. But if the bacteria are in a biofilm, the culture is negative.
“The medical community thinks blood is sterile, that urine and spinal fluid are free of bacteria,” Sauer says. “But that is not true. Biofilms are not necessarily floating around; they are quite stationary. So if you have an infection, you still don’t see bacteria floating around in the blood because biofilms avoid detection.”
“One of the best tricks that biofilms play, and also the most insidious, is they take advantage of microbiologists,” Davies says.
His colleagues chuckle but don’t disagree.
“When you say, for instance, we believe arthritis is a biofilm infection, the doctors counter with, ‘If this were a biofilm infection, you would see bacteria in the blood, elevated circulating white-cell numbers, you’d be able to take fluid from the joints and culture bacteria from them. And all of these come up negative, and therefore there can’t be a biofilm there.’
“We know better, because we know biofilms have a way of getting around these problems,” Davies says.
Two illnesses that are now accepted as bacterial in origin are otitis media (ear infections) and, most famously, stomach ulcers. The medical community routinely dismissed the theory of bacteria-induced ulcers until two Australian scientists proved that Helicobactyr pilori — a bacterium — was the cause. They won a Nobel Prize in 2005 for their discovery.
Davies believes biofilms are linked to atherosclerosis, which happens when fat and cholesterol clog the walls of the arteries and form plaques. Plaques can become dislodged and cause a heart attack or stroke.
“We believe it [atherosclerosis] is highly impacted by biofilm infections. We have direct evidence of bacteria growing inside people’s arteries,” Davies says. “What’s novel about the work that we’re doing is that we think hormones can influence the stability of the plaque deposit.”
This summer, Davies, Sauer and Bernard Lanter, a PhD candidate, had a paper on the topic published in mBio, the online, open-access journal of the American Society for Microbiology.
In it, the researchers explain that emotional or physical stress can trigger the body to release the hormone norepinephrine into the blood, which, in turn, may prompt biofilm dispersion in a diseased artery. The subsequent release of enzymes could weaken the inner arterial wall and lead to plaque rupture. Upon rupture, plaque enters the blood stream, forming a clot that blocks blood flow, causing a heart attack or stroke.
“We’re suggesting this is how you get scared to death,” Davies says.
He believes that Binghamton’s research might someday help rewrite medical books.
“We’re going one disease at a time and trying to demonstrate whether or not bacteria are involved. In most diseases ending with the letters -itis … it means inflammation, it means a biofilm infection.
“It’s important to appreciate how young this field is. Most of it is ahead of us.”