Simple Food Preservative Might Aid Chronic Cystic Fibrosis Sufferers
Published February 2006
Researchers led by a UC scientist say they have discovered what might be the "Achilles' heel" of a dangerous organism that lives in the lungs of cystic fibrosis patients--a fatal flaw that leaves the organism vulnerable to destruction by a common food preservative.
It has been known for some time that the bacterium, Pseudomonas aeruginosa, grows within the deadly, lung-clogging mucous found in the airways of cystic fibrosis patients and significantly weakens them.
The new study suggests, however, that a mutation--known as mucA--in the organism also represents a fatal flaw that could help physicians clear the characteristic "goop" from the lungs of advanced cystic fibrosis patients.
The reason for optimism, the researchers say, is that the same genetic change that turns Pseudomonas aeruginosa into a sticky, antibiotic-resistant killer also leaves it susceptible to destruction by slightly acidified sodium nitrite, a common chemical that is widely used in the curing of lunch meat, sausages and bacon.
The finding is reported in the February 2006 edition of the Journal of Clinical Investigation by a 15-member U.S. and Canadian team headed by Daniel Hassett, PhD, an associate professor in UC's molecular genetics, biochemistry and microbiology department. The research was funded by the U.S. National Institutes of Health, the Cystic Fibrosis Foundation and the U.S. Department of Energy.
"We believe that we have discovered the Achilles' heel of the formidable mucoid form of Pseudomonas aeruginosa, which could lead to improved treatment for cystic fibrosis airway disease," says Dr. Hassett. "We can essentially say that this organism, which some people thought could never be beaten, can now be destroyed by nothing more exotic than a common food preservative."
Cystic fibrosis, which affects about 30,000 people in the United States, is an inherited disease caused by a defect in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR).
Affecting the airways and many other vital organs and processes, cystic fibrosis is chronic, progressive and ultimately fatal, mostly as a result of respiratory failure.
Dr. Hassett and his colleagues found that about 87 percent of the mucoid Pseudomonas organisms they studied have the mucA flaw and can be easily destroyed by slightly acidified (pH 6.5) sodium nitrite.
Part of the problem with early and chronic cystic fibrosis, Dr. Hassett explains, is that patients with these conditions make very little nitric oxide, a derivative of acidified sodium nitrite.
"Pseudomonas aeruginosa bacteria should have enzymes that are able to dispose of both nitrite and nitric oxide," Dr. Hassett says, "but for whatever reason, the mutated bug doesn't make them, or has very few of them."
Dr. Hassett and his colleagues had worked on the hypothesis that the mucoid bacteria--because they flourish in patients who are essentially drowning in their own airway mucous--would grow better using nitrate or nitrite as an alternative to the missing oxygen. But when they tested nonmucoid and mucoid forms, the nonmucoids grew with both nitrate and nitrite without oxygen, while the mucoid organism grew only with nitrate, yet died with nitrite.
"Sodium nitrite kills the mucoids, and if nonmucoids or other bacteria are present in the airways, it inhibits their growth too," says Dr. Hassett.
Sodium nitrite, Dr. Hassett says, has potential as "a time-release" capsule for cystic fibrosis patients. Because the nitrite is degraded very slowly, and mucoid bacteria can't get rid of it, the chemical should specifically kill mucoid organisms that have the mucA mutation--which most do.
Dr. Hassett says he envisions sodium nitrite could be used in aerosol form to treat mucoid Pseudomonas aeruginosa in cystic fibrosis lung disease.
"This wouldn't need to be a long-term treatment," he says. "Once a patient acquires mucoids, which commonly occur, the physician would simply use sodium nitrite and monitor how many mucoid bacteria are still in airway sputum. Once the mucoid organisms are killed, and the patient starts showing signs of improvement, treatment would continue with conventional antibiotics."
But bringing this treatment to the bedside won't be easy, Dr. Hassett concedes.
"Right now, we don't see the Food and Drug Administration approving blowing sodium nitrite into people's airways, because it may potentially have some toxic side effects."However, nitrites are used clinically to counteract cyanide poisoning, warts and athlete's foot, for example. And in neonatal pulmonary hypertension, physicians may be using nitrite doses nearly 60 times higher than we use to kill the organism in mouse and human airway cells."