Sneezing, snoring, and bouts of runny nose are the hallmarks of cold and flu season — and that increase in mucus is exactly what bacteria use to launch a coordinated attack on the immune system, according to a new study by researchers at Penn State. The team found that the thicker the mucus, the better the bacteria can accumulate. The findings could have implications for treatments that reduce the bacteria’s ability to spread.
The study, recently published in the journal PNAS Nexus, shows how bacteria use mucus to enhance their ability to self-organize and possibly drive infection. The experiments, carried out using synthetic pig stomach mucus, natural cow cervical mucus and a water-soluble polymer compound called polyvidone, revealed that the bacteria coordinate movement better in thick mucus than in aqueous substances.
The findings provide insight into how bacteria colonize mucus and mucosal surfaces, the researchers said. The findings also show how mucus enhances the collective movement of bacteria, or swarming, which can increase the resistance of bacterial colonies to antibiotics.
“To our knowledge, our study is the first demonstration of bacteria swimming collectively in mucus,” said Igor Aronson, Professor of Biomedical Engineering, Chemistry and Mathematics at Penn State and corresponding author of the paper. “We have shown that mucus, unlike liquids of similar composition, enhances collective behavior.”
Mucus is essential for many biological functions, Aronson explained. It coats the surfaces of cells and tissues and protects against pathogens such as bacteria, fungi and viruses. But it is also the host material for bacterial-born infections, including sexually transmitted and gastric diseases. A better understanding of how bacteria swarm in mucus could pave the way for new strategies to fight infections and the growing problem of antibiotic resistance, according to Aronson.
“Our findings show how mucus cohesion affects the random movement of individual bacteria and affects their transition to coordinated, collective movement of large bacterial groups,” Aronson said. “There are studies showing that collective movement or swarming of bacteria enhances the ability of bacterial colonies to resist the effect of antibiotics. The initiation of the collective behavior studied in our work is directly related to swarming.”
Mucus is an extremely challenging substance to study because it exhibits both liquid and solid properties, Aronson explained. Liquids are typically described by their level of viscosity, how thick or thin the liquid is, and solids are described by their elasticity, how much force it can take before breaking. Mucus, a viscoelastic fluid, behaves as both a liquid and a solid.
To better understand how mucus becomes infected, the team used microscopic imaging techniques to observe the collective movement of concentrated Bacillus subtilis bacteria in synthetic pig stomach mucus and natural cow cervical mucus. They compared these results with observations of Bacillus subtilis moving on a water-soluble polyvidone polymer over a wide range of concentrations, from high to low levels of polyvidone. The researchers also compared their experimental results with a computational model for the collective movement of bacteria in viscoelastic fluids such as mucus.
The team found that the consistency of the mucus profoundly affects the collective behavior of the bacteria. The results showed that the thicker the mucus, the more likely the bacteria are to show collective movement, forming a coordinated swarm.
“We were able to show how viscoelasticity in mucus enhances bacterial organization, which in turn leads to coherent movement of bacterial groups that cause infection,” Aronson said. “Our results reveal that the levels of elasticity and viscosity in mucus are a major driver of how bacterial communities are organized, which may provide insights into how we can control and prevent bacterial invasion of mucus.”
Aronson explained that the team expected human mucus to exhibit similar physical properties, meaning their findings are also relevant to human health.
“The initiation of bacterial collective movement and their interaction with mucus should be the same as in cow, pig or human mucus, as these substances have similar mechanical properties,” Aronson said. “Our results have implications for human and animal health. We show that mucus viscoelasticity can enhance the large-scale collective movement of bacteria, which can speed up how quickly bacteria penetrate the protective mucus barrier and infect internal tissues .”
The other co-author on the paper is Wentian Liao, a doctoral candidate in biomedical engineering at Penn State. The National Science Foundation supported the project.