Breaking Through Protective Barrier Of Bacteria

At first, her interest was purely professional. As a physicist, Eleonora Secchi has long been interested in how soft materials behave under mechanical stress - that is, when they are strained or pulled. She first became aware of biofilms during a conversation with a fellow engineer. Biofilms are slime-like structures formed by bacteria. They colonise damp surfaces, both in technical systems and in our bodies. Biofilms can be found in water pipes, for example, or as plaque in our mouths. They can clog water filters, but they can also cause tooth decay or persistent infections in our bodies.

That's why Eleonora Secchi's interest in the topic is not only professional, it's also personal. Her mother suffers from a chronic infection caused by biofilms. "Seeing how difficult the disease is to treat gives me extra motivation in my research," says Secchi. Her goal is to be able to effectively combat biofilms wherever they pose a threat.

How a matrix protects bacteria

To do this, scientists must first gain a better understanding of biofilms. Physics can play a key role here, as biofilms have very specific physical properties. Rather than simply clumping together, the bacteria actively create a stable matrix that holds them together. This gel-like matrix forms a fortress-like protective barrier that shields the bacteria from the outside world. True to the saying "There's strength in numbers", bacteria within biofilms support each other, by cooperating to process nutrients and produce components for the matrix, for example.

Biofilms are not always harmful. They are found on the mucous membranes in our noses, in our intestines and on our skin, for example. These communities of bacteria don't usually pose any threat to us; in fact, they perform important tasks, such as warding off pathogens or aiding digestion. It's a different story when pathogenic bacteria form biofilms. "An estimated 60 to 80 per cent of all infections are caused by biofilms," says Secchi.

The matrix is what often makes these bacteria difficult to fight off. Immune cells and antibiotic agents both have a hard time penetrating the protective shield. Bacteria are much better protected in a biofilm than they would be as individual cells. Biofilms therefore cause a great deal of suffering and high costs. That's because they can colonise ventilation tubes or joint prostheses during operations, for example. These kinds of medical devices are difficult to clean and costly to replace.

Biofilms harden in a current

Eleonora Secchi and her team primarily investigate biofilms in flowing fluids, under conditions that mimic those found in places ranging from water hoses to the urinary tract. Under these conditions, biofilms can form so-called "streamers": long, thread-like structures that protrude into the flow. The flowing liquid provides them with a constant supply of new nutrients. On the other hand, the current exerts mechanical stress on the bacteria because they are constantly at risk of being washed away. "In response to this, streamers exhibit a particular behaviour: they harden and become stiffer," says Secchi. This makes it even more difficult to remove disruptive or pathogenic bacterial communities.

To study the behaviour of streamers, the researchers used microfluidic technology that allows the creation of artificial mini-worlds which replicate the conditions in a blood vessel or water pipe in the lab. This allowed Secchi's team to gain valuable insights and, in a recently published external page paper , to demonstrate for the first time how streamers harden. They were surprised by what they found: "Previously, it had been assumed that biofilms adapt to the stress caused by a current biologically. In other words, that bacteria use molecular sensors to explore their environment and actively respond to it by changing the matrix composition," says Secchi. But that's not what happens: "Hardening is a purely passive, physical mechanism."

A specific component of the matrix, known as extracellular DNA, plays a key role in this process. Alongside sugar molecules and proteins, this is an essential building block in biofilms. It acts as a physical backbone, helping to strengthen the matrix. This was also a surprise: "Human cells and bacteria both produce extra-cellular DNA constantly. However, this is not only a carrier of genetic information; bacteria also actively use it in biofilms as a building material for their protective fortress," says Secchi.

Breaking down the strongest defences

Using these new findings, Eleonora Secchi wants to try to weaken the protective shield of biofilms. The idea is to make the matrix more permeable so that it is easier to remove and more vulnerable to existing treatments. For Secchi, one thing is clear: "There is no single best way to attack biofilms. We should use different strategies simultaneously." This also includes washing away biofilms or attacking them chemically.

Next, Secchi and her team, with the support of the Swiss National Science Foundation, will investigate whether other forms of biofilms besides streamers also utilise stress-induced hardening as a protective mechanism. Perhaps this is a fundamental principle of how biofilms adapt to environmental conditions. At the same time, the group is investigating when and how drugs such as antibiotics manage to penetrate biofilms. "Understanding the physical defence mechanisms of biofilms better won't make antibiotics redundant. But it can help make treatments more effective by weakening one of the strongest defence strategies the bacteria use," says Secchi.