Modeling a Strategy to Storm a Biofilm’s Walls

As a celebrated chaos theory scientist once observed, “Life, uh, finds a way.” Perhaps nowhere else in the world’s vast taxonomy is that tenet more evident than in the constant battle of microbes, both with each other and their environments.

In one small but important example, the bacteria Pseudomonas aeruginosa can protect itself from the antibiotics doctors use to treat it. Infestation of the lungs by a film of P. aeruginosa is a common ailment for people living with cystic fibrosis, a genetic disorder leading to a median lifespan of just 48 years.

The reasons behind the antibiotics’ inability to clear the bacterial infection, however, remain shrouded in mystery. Some researchers believe it’s a straightforward matter of natural diffusion limitations of the medicine spreading through the infection. Others think that the bacteria cover themselves in a layer of DNA, their internal replication machinery, to keep the antibiotics at bay. Either way, recent research indicates that the electrical charge of the antibiotics plays a key role.

A-Andrew Jones, assistant professor of civil and environmental engineering at Duke University, builds mathematical models to help find the true nature of their strategies so that modern medicine can thwart the microbes’ defenses. Jones and PhD student Joshua Prince have developed a realistic reenactment of the physical phenomena that lead to the biofilm’s defenses, depicted in a claymation video.

“The model is showing us that spatial differences in where the bacteria secrete antibiotic-trapping polymers is an important aspect of their defenses,” said Jones. “It’s giving credence to the theory that the bacteria are using their DNA—either on purpose or by happenstance—to trap the antibiotics and keep it out of the biofilm’s interior.”

Prince describes the battle for survival like scenes from the zombie movie “World War Z.” Like vast hordes of the undead climbing on top of one another to get over defensive walls, antibiotics can breach a biofilm’s interior if enough of it is deployed. Their model, he says, might help clinicians tailor the dosage to use just enough to kill off the infection without raising the risk of the bacteria developing additional antibiotic resistance.

“Whether the bacteria are responding to the antibiotics’ electrical charge or some other facet, our model shows that their spatial organization really matters,” Prince said. “With more information about the biofilm’s structure, we might also be able to formulate a nanoparticle that can carry the antibiotics past the biofilm’s defensive wall.”

Citation: Prince, J. and A.A.D. Jones (2023). “Heterogenous biofilm mass-transport model replicates periphery sequestration of antibiotics in Pseudomonas aeruginosa PAO1 microcolonies.” Proceedings of the National Academy of Sciences 120(47): e2312995120.