New research zooms in on Pseudomonas aeruginosa to uncover a strategy that drug-resistant bacteria use to avoid antibiotics. The findings could help make antibiotics more effective.

Jean-Louis Bru, from the department of molecular biology and biochemistry at the University of California, Irvine, is the first author of the new study, which appears in the Journal of Bacteriology.

Bru and colleagues focused their research efforts on Pseudomonas aeruginosa (P. aeruginosa), a type of bacteria that attacks people with cystic fibrosis.

Cystic fibrosis is a hereditary respiratory condition wherein the lungs produce more mucus than they should. It affects about 30,000 people in the United States.

P. aeruginosa is one of the most dangerous types of bacteria.

In the context of the public health crisis that is antibiotic resistance, the World Health Organization (WHO) placed P. aeruginosa on the list of "priority pathogens"—that is, the 12 bacteria that are most hazardous to human health because they have become resistant to the drugs that doctors commonly used to fight them.

WHO divided these 12 bacteria into "critical," "high," and "medium" priority, listing P. aeruginosa as critical due to its resistance to the group of antibiotics called carbapenems.

In this broader picture, research such as the study that Bru and colleagues have conducted is crucial for both understanding bacteria's defense mechanisms and tackling infections more effectively.

Bacteria act as 'one united organism'

In the new study, the researchers examined the growth and spread of bacteria in petri dishes, recreating an environment similar to that of the mucous membranes that enable P. aeruginosa to thrive in cystic fibrosis.

Here, the team tested the effect of antibiotics and bacteriophages on "swarming," which is the ability that bacteria have to move collectively. Bacteriophages are viruses that infect and attack bacteria from within.

Mixing the antibiotic gentamicin with P. aeruginosa cells revealed that the bacteria send signals to their conspecific bacteria, warning them of the danger and enabling them to avoid it.

The Pseudomonas bacteria do this by secreting the quinolone signaling molecule PQS, write the authors. They explain, "These mechanisms have the overall effect of limiting the infection to a subpopulation, which promotes the survival of the overall population."

Study co-author Nina Molin Høyland-Kroghsbo, an assistant professor at the department of veterinary and animal sciences at the University of Copenhagen in Denmark, comments on the experiments and their findings.

"We can see in the laboratory that the bacteria simply swim around the 'dangerous area' with antibiotics or bacteriophages. When they receive the warning signal from their conspecifics, you can see in the microscope that they are moving in a neat circle around," the researcher says, referring to the swarming motion.

"It is a smart survival mechanism for the bacteria," she continues. "If it turns out that the bacteria use the same evasive maneuver when infecting humans, it may help explain why some bacterial infections cannot be effectively treated with antibiotics."

"It is quite fascinating for us to see how the bacteria communicate and change behavior in order for the entire bacterial population to survive. You can almost say that they act as one united organism."

—Nina Molin Høyland-Kroghsbo

Paving the way for more effective antibiotics

In a linked editorial, Julia C. van Kessel comments on the significance of the findings, saying that P. aeruginosa's ability to affect a group behavior, such as swarming in response to stress, is a "unique" finding. This led the study authors to coin the term "collective stress response," writes van Kessel.

The study authors also comment on ways in which their findings could ultimately help tackle the antibiotic resistance crisis.

Although there is a lot more work to do before the findings lead to the development of helpful treatments, the next research step will be to find ways to interfere with the bacteria's PQS signaling.

The findings "[clear] the way for the use of drugs in an attempt to prevent that the warning signal is sent out in the first place," says Nina Molin Høyland-Kroghsbo.

"Alternatively, you could design substances that may block the signal from being received by the other bacteria, and this could potentially make treatment with antibiotics or bacteriophage viruses more effective," adds the researcher.

"Infections with this type of bacteria are a major problem worldwide, with many hospitalizations and deaths. That is why we are really pleased to be able to contribute new knowledge that can potentially be used to fight these bacteria."

—Nina Molin Høyland-Kroghsbo