DNA sequencing may help revolutionize CF lung infection care: Study
Technology could pave way for faster, more precise, personalized treatment
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Cutting-edge DNA sequencing technologies for microbial surveillance have the potential to revolutionize how lung infections in people with cystic fibrosis (CF) are diagnosed and managed, according to a new review study.
However, researchers noted that there are still challenges that need to be overcome before these technologies can be adopted into widespread clinical tools.
DNA sequencing, a technique to determine the sequence of DNA’s building blocks within a piece of DNA, is “transforming how we diagnose and manage infections, revealing entire microbial communities instead of single [microbes] and paving the way for faster, more precise, and personalised treatment,” Rob Edwards, PhD, the study’s senior author and a professor at Flinders University in Australia, said in a university news story.
Jessica Carlson-Jones, PhD, the study’s first author, also from Flinders, said this technology “is a powerful tool which can monitor these microbial changes, detect infections more rapidly than traditional laboratory methods and identify antimicrobial resistance.”
The review study, “DNA sequencing for microbial surveillance in cystic fibrosis airways: advances, challenges, and clinical translation,” was published in Clinical Microbiology Reviews.
Technique looks at DNA from all the organisms in a sample
CF is a disease caused by mutations in the gene that encodes CFTR, a protein that’s vital for normal mucus production. These mutations lead to the production of unusually thick, sticky mucus that, in the lungs, provides a safe haven for infectious bacteria, fungi, and viruses (pathogens).
Consequently, lung infections are a common and serious health problem in people with CF, with a high risk of developing infections that become resistant to several antimicrobial treatments.
Traditionally, lung infections are identified using culture methods, where a sample collected from the patient’s airway mucus or fluid is taken to a laboratory to see what types of infection-causing bacteria or fungi can be grown from the sample.
Although it’s long been the mainstay, this approach has some notable disadvantages. In addition to being time-consuming, culture-based methods can usually only identify certain types of microbes.
This makes it virtually impossible to get a comprehensive view of the complex community of microorganisms that live in the airways, which include not only pathogens but also other microscopic organisms that do not cause disease and may in fact be important for maintaining healthy lungs.
For instance, metagenomics, a DNA sequence technique that looks at the DNA from all the organisms in a sample, offers a key alternative because it allows researchers to identify all microorganisms in a sample.
“Rather than viewing cystic fibrosis infections as being caused by a single pathogen, sequencing has revealed that lungs contain complex microbial communities of bacteria, viruses and fungi, which influence disease progression and treatment response,” Edwards said. As such, DNA sequencing can “be very effective in understanding lung infections, particularly in cystic fibrosis.”
Sequencing tech already being used to guide clinical care
In some parts of the world, these cutting-edge sequencing technologies, which may also allow the detection of genes providing resistance to antimicrobial treatment, are already being used to help guide clinical care.
“Respiratory metagenomic sequencing is already being introduced into intensive care units in the UK to provide faster diagnosis of severe respiratory infections and guide antimicrobial therapy,” Carlson-Jones said. “It will take further testing for sequencing to become part of routine clinical practice in Australia, but it has great promise in transforming the diagnosis and management of infectious diseases as well as cystic fibrosis.”
She also noted that Australian researchers are also working to develop portable sequencing devices that could be used in hospitals, even in remote areas.
Still, the researchers emphasized there are several obstacles standing in the way of widespread adoption of these cutting-edge techniques. For one thing, these new technologies tend to be pricey, making access a challenge in many parts of the world. There are also technical challenges, such as differentiating between microbial DNA and DNA from the person being tested.
As sequencing technologies evolve, they hold increasing potential for real-time pathogen surveillance, personalised antimicrobial therapy and further improvement in CF clinical care and other microbial driven conditions.
And although having an overarching view of all microorganisms in a sample can theoretically offer great insight, figuring out how to translate these massive data sets into clinically actionable findings also remains a challenge.
“As sequencing technologies evolve, they hold increasing potential for real-time pathogen surveillance, personalised antimicrobial therapy and further improvement in CF clinical care and other microbial driven conditions,” Carlson-Jones said.
In addition to improving infection management, sequencing may provide new glimpses into how CF treatments, such as CFTR modulator therapies, affect communities of microorganisms in the lungs.
“While these life-changing therapies have improved the quality of life for many people with cystic fibrosis, researchers are still uncovering how they reshape the airway microbiome over time,” Carlson-Jones said.
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