A New Study Method for P. aeruginosa May Accelerate CF Research

Researchers are finding ways to better understand infection in cystic fibrosis, enabling research efforts that help discover treatments for patients. Dr. Marvin Whiteley at The University of Texas at Austin created a platform to study Pseudomonas aeruginosa, the most common cause of hospitalization and illness for cystic fibrosis patients. Their work was published in Proceedings of the National Academy of Sciences.

“We’ve developed something other labs can replicate,” said Dr. Whiteley, in a news release. “It allows researchers to do relevant experiments in a context that really matters.” He has used this simulation technique for over five years. Scientists mapped the genome of P. aeruginosa 15 years ago, but few have researched how targeting P. aeruginosa genes may lead to a new avenue of research.

One reason for the gap in knowledge is the difficulty of replicating the environment of a cystic fibrosis patient’s lungs in order to understand P. aeruginosa behavior in its infective habitat. Models of bacteria in cultures of mammalian cells have shown that P. aeruginosa acts differently when in the lungs of a patient.

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Unsurprisingly, the best model of a human lung to study P. aeruginosa consisted of mucus secretions from cystic fibrosis patients. As described in their paper, “Essential Genome of Pseudomonas aeruginosa in Cystic Fibrosis Sputum,” Dr. Whiteley’s team first used computer simulations to analyze high-throughput genetic data to determine the genes that are essential for P. aeruginosa to thrive in plain cell culture medium or cystic fibrosis patient sputum. The researchers found core genes were shared between two strains of bacteria, although the team identified that genes pertaining to similar molecular functions could have different implications in the two strains. Taking this knowledge from the computer to the laboratory, the team validated that their computer model describes actual P. aeruginosa activity in medium and sputum.

Other researchers are interested in Dr. Whiteley’s research. “For the past decade, we have understood that Pseudomonas is arguably the major colonizing infection for people with cystic fibrosis,” acknowledged John LiPuma, MD, a professor of pediatrics and epidemiology at the University of Michigan. “For a long time we have studied Pseudomonas the way we study other pathogens. But the cystic fibrosis lung is extraordinarily complex. In the research community, we’ve got to develop systems biology approaches, such as this one, that take a more sophisticated approach to get us where we need to be.”

Dr. Whiteley’s research is differentiated from others’ work in that it uses real-life growing conditions. “Most studies grow bacteria in test tubes in a rich growth medium they never see in the real world,” said Dr. Steve Diggle, an associate professor of life sciences at the University of Nottingham. “It’s rather like studying lion behavior in a zoo rather than in its natural habitat. What Marvin has done is to try and re-create the sputum that Pseudomonas grows in so we can see what genes are important for bacterial fitness in this environment.”

Understanding P. aeruginosa is important because it is dangerous especially to cystic fibrosis patients. The bacteria congregates within the lungs inside a thick layer of mucus to form large colonies that usually develop resistance to antibiotics. Once infected, patients (usually in their childhood) have difficulty breathing due to the high degree of inflammation in the lungs. Studying the bacteria in its natural habit may translate to more effective therapies.