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Microbe DNA Discovery May Lead to Noninvasive Test for CF Infections

People with cystic fibrosis (CF) have higher levels of DNA from common microbes that cause CF-related infections circulating in their blood compared to healthy controls, a study discovered.

These findings support the development of a simple blood test as a noninvasive diagnostic tool to identify chronic lung infections in CF patients.

CF is marked by chronic airway infection. Accurately diagnosing and monitoring the start of infection can be challenging, especially in children who often are unable to provide regular sputum samples, and also for those on effective therapies that reduce sputum production.

A new type of biomarker in infectious disease diagnosis comes from DNA released into the blood by decomposing cells called cell-free DNA (cfDNA).

Most cfDNA comes from a person’s own cells, but a small amount of microbial DNA has been detected effectively in the blood during acute infections, particularly from microorganisms that directly invade the bloodstream.

Given that some CF-related microbes can be invasive and inflammation can lead to tissue damage, cfDNA originating from lung microbes may enter the bloodstream of CF patients during chronic infection.

To find out if this occurs, researchers at the University of Washington in Seattle collected blood samples from 21 people with CF, ages 19 to 62. Blood from 12 healthy people of similar age was collected as controls. cfDNA was isolated and sequenced to identify its microbial source.

The analysis revealed that the amount of microbial cfDNA — from organisms that commonly infect the lungs of CF patients — was nearly 10 times higher in the blood of CF patients compared to healthy controls. Of the 21 CF patients, 15 had cfDNA from one or more organisms at significantly higher levels.

In contrast, none of the healthy control subjects had higher levels of microbial cfDNA for any of the selected organisms.Microorganisms also were cultured and identified from sputum samples collected from patients to compare each method. From these, a total of 44 identified microbial infections were found, and 15 of those statistically matched the cfDNA results.

For some bacteria, the cfDNA and the sputum results matched perfectly, while with others it did not. In particular, out of 13 Pseudomonas aeruginosa infections identified in sputum, eight were confirmed by cfDNA, while 12 infections by Staphylococcus aureus were found in sputum samples, compared to four by cfDNA.

Conversely, 17 identified microbial infections (from 11 patients) using cfDNA were not identified by sputum culture, including Burkholderia cepacia and Mycobacterium species. “These results could represent true infection which was not diagnosed by sputum culture,” the researchers wrote.

While the results from the cfDNA analysis did not perfectly match those from the sputum cultures, with some infections identified by one method or the other, the study authors pointed out that sputum culture identification can be inconsistent, and not all organisms recovered by this method are actively involved in the disease.

“Our findings indicate that cfDNA from relevant microbes are detectable from the circulation of CF patients at statistically greater abundance than unaffected individuals,” the researchers wrote. “Our results provide evidence that plasma cfDNA from airway pathogens has the potential to be used in the noninvasive diagnosis of at least some chronic CF lung infections.”

Nonetheless, the team noted that “additional work involving larger cohorts [groups] monitored longitudinally [over time] will be needed to refine and validate methods, to establish the performance characteristics of cfDNA in identifying specific pathogens, [and] to compare cfDNA to … sputum testing methods.”

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