Protecting the lung's 'ecosystem' may help cystic fibrosis patients.
Viewing the lungs of patients with cystic fibrosis as troubled ecosystems that need to be managed may lead to new ways of treating bacterial infections, a team of US researchers suggests.
People with cystic fibrosis have two mutated genes, one inherited from each parent, which make the mucus in their lungs abnormally sticky. This clogs up the hair-like cilia that move mucus — and any microbes trapped in it — up and out of the lungs. As a result, patients are very susceptible to lung infections and many die of respiratory complications before they reach the age of 40.
According to the traditional medical view, healthy lungs are nearly sterile and any microbes are dangerous pathogens that need to be wiped out. So treatment of cystic fibrosis is heavy on antibiotics, both oral and inhaled. Now, a team of researchers led by Vanja Klepac-Ceraj of Harvard Medical School in Boston, who have followed 45 young patients with cystic fibrosis, are challenging that view.
Presenting the team's work on 5 August at the annual meeting of the Ecological Society of America in Albuquerque, New Mexico, Klepac-Ceraj said they found that the microbial communities in some of their subjects' throats are diverse, similar to the communities in the throats of healthy people. Other patients, who are often older and more unwell, show simpler, more unique communities that tend to have one thing in common: the presence of Pseudomonas aeruginosa — a bacterium that can cause deadly lung infections in these patients that are difficult to treat.
When looking at these communities of microbes as ecosystems, Klepac-Ceraj says, P. aeruginosa can be seen as an invasive species — an aggressive and unwanted bacterium that can outcompete more benign microbes. And a course of antibiotics can be seen as an ecosystem disturbance, something like a wildfire in a forest ecosystem. Klepac-Ceraj worries that antibiotic disturbance, as is well known from plant communities, actually makes it easier for an invasive species such as P. aeruginosa to become well established.
"These patients are often given antibiotics even before they acquire Pseudomonas," says Klepac-Ceraj. Indeed, cystic fibrosis experts say that there has been concern in the field for some time about hastening Pseudomonas infection by overusing antibiotics.
In the future, therapies that are modelled on strategies to combat invasive species might prove to be useful. For example, some invasive species are tackled by introducing their native predators to their new haunts — ecologists in Hawaii, for instance, are hoping to beat back invasive strawberry guava, a native of Brazil, with a Brazilian scale insect that forms galls on its leaves and saps its energy.
In the same way, viruses that infect bacteria, called bacteriophages, could someday be used to target specific members of the microbial community in patients with cystic fibrosis — but not necessarily P. aeruginosa itself, suggests Peter Greenberg, a microbiologist at the University of Washington in Seattle.
"We might want to go after species that are not pathogens themselves but that signal Pseudomonas to do more damage," Greenberg says.
Or perhaps avoiding antibiotics could encourage more benign microbes to grow which might protect against infection by Pseudomonas. "By looking at microbial communities as a whole, we can understand what is happening when we treat them with antibiotics and see if there are any members that, by being removed, make the whole community more susceptible to Pseudomonas invasion or some other pathogen," explains Klepac-Ceraj.
Gerald B. Pier of Harvard Medical School, who also studies P. aeruginosa, feels that it is "too early to embrace any strategies to manage ecosystems" to combat lung infections in cystic fibrosis. "While the diversity in ecosystems is interesting, it is probably more of a reflection of the presence of Pseudomonas than anything else," says Pier. "Preventing and treating Pseudomonas is, at this stage, the clear goal for improving the clinical condition of cystic fibrosis patients."
Klepac-Ceraj hopes to follow her patients for five years, looking for further correlations between disease progression and microbial communities. In addition, the team will look at how variants of cystic fibrosis caused by different mutated genes affect microbial composition.