Bacterial cells in solutions of polymers such as mucus grow into long cable-like structures that buckle and twist on each other, forming a “living gel” made of intertwined cells. This behaviour is very different from what happens in polymer-free liquids, and researchers at the California Institute of Technology (Caltech) and Princeton University, both in the US, say that understanding it could lead to new treatments for bacterial infections in patients with cystic fibrosis. It could also help scientists understand how cells organize themselves into polymer-secreting conglomerations of bacteria called biofilms that can foul medical and industrial equipment.
Interactions between bacteria and polymers are ubiquitous in nature. For example, many bacteria live as multicellular colonies in polymeric fluids, including host-secreted mucus, exopolymers in the ocean and the extracellular polymeric substance that encapsulates biofilms. Often, these growing colonies can become infectious, including in cystic fibrosis patients, whose mucus is more concentrated than it is in healthy individuals.
Laboratory studies of bacteria, however, typically focus on cells in polymer-free fluids, explains study leader Sujit Datta, a biophysicist and bioengineer at Caltech. “We wondered whether interactions with extracellular polymers influence proliferating bacterial colonies,” says Datta, “and if so, how?”
Watching bacteria grow in mucus
In their work, which is detailed in Science Advances, the Caltech/Princeton team used a confocal microscope to monitor how different species of bacteria grew in purified samples of mucus. The samples, Dutta explains, were provided by colleagues at the Massachusetts Institute of Technology and the Albert Einstein College of Medicine.
Normally, when bacterial cells divide, the resulting “daughter” cells diffuse away from each other. However, in polymeric mucus solutions, Datta and colleagues observed that the cells instead remained stuck together and began to form long cable-like structures. These cables can contain thousands of cells, and eventually they start bending and folding on top of each other to form an entangled network.
“We found that we could quantitively predict the conditions under which such cables form using concepts from soft-matter physics typically employed to describe non-living gels,” Datta says.
Support for bacterial colonies
The team’s work reveals that polymers, far from being a passive medium, play a pivotal role in supporting bacterial life by shaping how cells grow in colonies. The form of these colonies – their morphology – is known to influence cell-cell interactions and is important for maintaining their genetic diversity. It also helps determine how resilient a colony is to external stressors.
“By revealing this previously-unknown morphology of bacterial colonies in concentrated mucus, our finding could help inform ways to treat bacterial infections in patients with cystic fibrosis, in which the mucus that lines the lungs and gut becomes more concentrated, often causing the bacterial infections that take hold in that mucus to become life-threatening,” Datta tells Physics World.
Friend or foe?
As for why cable formation is important, Datta explains that there are two schools of thought. The first is that by forming large cables, bacteria may become more resilient against the body’s immune system, making them more infectious. The other possibility is that the reverse is true – that cable formation could in fact leave bacteria more exposed to the host’s defence mechanisms. These include “mucociliary clearance”, which is the process by which tiny hairs on the surface of the lungs constantly sweep up mucus and propel it upwards.
“Could it be that when bacteria are all clumped together in these cables, it is actually easier to get rid of them by expelling them out of the body?” Dutta asks.
Investigating these hypotheses is an avenue for future research, he adds. “Ours is a fundamental discovery on how bacteria grow in complex environments, more akin to their natural habitats,” Datta says. “We also expect it will motivate further work exploring how cable formation influences the ways in which bacteria interact with hosts, phages, nutrients and antibiotics.”
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