Developing a New Treatment for Cystic Fibrosis

Researching Bacterial Cheaters to Help Cure Chronic Lung Disease

Sep 8, 2009

Research on microbes that cheat during quorum sensing may give scientists a novel weapon against bacteria that cause serious health problems in Cystic Fibrosis patients.

Nobody likes a cheater. Whether it’s cheating on taxes, playing Monopoly, or even just cutting in line at the grocery store, someone that plays his fellows for fools is sure to make only enemies.

What Makes a Bacterial Cell a Cheater?

The same goes for bacteria. Many bacteria communicate with each other through a process called quorum sensing. In some cases, quorum sensing is necessary to break down food for survival. The cells constantly tell each other where they are by sending and receiving small compounds, like a never-ending game of Marco Polo, the classic swimming pool game of tag. A cell that receives enough of this signal normally secretes enzymes to help the group break down local food into small chunks that can then be brought inside individual cells.

This is where the cheaters come in. In bacteria, a cheater can be defined as simply a cell that does not emit the costly enzyme, even though it received the signal to do so. This cell gets to reap the benefits of the other hard-working cells, taking in food as fast as the others break it down, while the others waste time and energy making Marco Polo compounds and ejecting enzymes.

Bacterial Cheaters in the Lung

New research suggests that targeting quorum sensing in certain bacteria may one day be an alternative treatment for bacterial infections, particularly in cystic fibrosis patients. The studies show that quorum sensing is important for Pseudomonas aeruginosa, a usually harmless species of bacteria that can occasionally cause very serious health problems. When enough cheaters enter a population of this bacteria, quorum sensing breaks down, and the group can eventually starve. The new idea from the experiments is that if quorum sensing cheaters can bring about the downfall of the bacterial community, then perhaps ingested drugs or compounds could too. The research was published in autumn 2007 by two independent scientists, Martin Schuster of the University of Oregon and Steve Diggle of the University of Nottingham, in the journal Proceedings of the National Academy of Sciences and the journal Nature, respectively.

What is Cystic Fibrosis?

Cystic fibrosis is a life-threatening pulmonary disease that affects 30,000 Americans. According to the Cystic Fibrosis Foundation, around 1,000 new cases of cystic fibrosis are diagnosed each year. The disease is a genetically recessive one, so though it takes two copies of the defective gene to actually suffer from the disorder, ten million Americans are carriers for the disease. Less than 60 percent of individuals afflicted with cystic fibrosis live past age 18. There is currently no cure.

Persons with cystic fibrosis have mucous buildup in their lungs and other organs, and this excess mucous can cause bacteria to get caught in normally sterile airways and establish chronic infections. Pseudomonas is one of these bacteria, and with its unusually large genome that enables it to constantly thwart the human immune system, it is well adapted to life in cystic fibrosis patients. These particular bugs are also capable of developing resistance to almost every kind of antibiotic available. It is after colonization by Pseudomonas aeruginosa that the lungs of a cystic fibrosis patient usually go from bad to worse.

The Role of Quorum Sensing in Cystic Fibrosis

“Quorum sensing is thought to be involved in biofilm formation,” says Diggle. Biofilms are mat-like bacterial communities, often composed of several different species of microbes. This diversity often makes the bacteria in biofilms hard to kill. “The idea of inhibiting quorum sensing,” explains Diggle, “is that you make a weaker biofilm that is more easily cleared.” This would return some lung capacity to a cystic fibrosis victim, making everyday life easier.

But it’ll be a few more years before this new knowledge makes it to clinical trials. In the meantime, Diggle hopes to see clinical work examining how the cheater to non-cheater ratio might change over time in a cystic fibrosis patient’s lung. “I think the ecology needs to be studied in more detail,” Diggle says. The difficulties of applying abstract laboratory work to clinical studies are many. Concludes Diggle, “Going from the flask to the lung is a massive leap.”

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