Adelaide, Australia – Advanced DNA sequencing technologies could significantly improve the detection, monitoring, and treatment of lung infections in people with cystic fibrosis (CF), according to a recent review published in Clinical Microbiology Reviews. These approaches can provide a more comprehensive picture of the microorganisms present in the airways than conventional diagnostic methods, potentially enabling faster and more personalized treatment.
However, several technical, clinical, and economic challenges must still be addressed before sequencing can become part of routine clinical care.
The review, titled “DNA sequencing for microbial surveillance in cystic fibrosis airways: advances, challenges, and clinical translation,” examined recent advances in sequencing-based approaches to microbial surveillance and their potential applications in CF care.
Limitations of traditional methods for detecting lung infections
Cystic fibrosis is caused by mutations in the gene encoding CFTR, a protein essential for maintaining normal mucus production. These mutations result in unusually thick and sticky mucus, particularly in the lungs, creating an environment in which disease-causing bacteria, fungi, and viruses can persist.
As a result, recurrent and chronic lung infections are a major health concern for people with CF. These infections can also become resistant to multiple antimicrobial treatments, making rapid and accurate identification of the microorganisms involved particularly important.
Traditionally, respiratory infections have been diagnosed using culture-based methods. Samples of airway mucus or fluid are collected and sent to a laboratory, where clinicians attempt to grow and identify bacteria or fungi that may be responsible for an infection.
Although culture remains an important diagnostic tool, it has significant limitations. The process can be time-consuming, and many microorganisms cannot be readily detected using standard culture techniques. Consequently, culture-based testing provides only a partial picture of the complex microbial communities inhabiting the airways.
These communities include not only disease-causing pathogens but also microorganisms that may be harmless or potentially beneficial to lung health.
Sequencing reveals the broader airway microbiome
DNA sequencing offers a way to overcome some of these limitations. Metagenomic sequencing, for example, analyzes genetic material from all organisms present in a sample rather than searching for a specific microorganism.
This approach can reveal the diverse communities of bacteria, viruses, and fungi that collectively make up the airway microbiome.
“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,” said Rob Edwards, PhD, senior author of the review and a professor at Flinders University in Australia.
According to Edwards, DNA sequencing 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.”
Jessica Carlson-Jones, PhD, the study’s first author and also a researcher at Flinders University, highlighted another important advantage: sequencing can potentially identify infections more quickly while simultaneously providing information about antimicrobial resistance.
She described sequencing as “a powerful tool which can monitor these microbial changes, detect infections more rapidly than traditional laboratory methods and identify antimicrobial resistance.”
Together, these capabilities could help clinicians determine not only which microorganisms are present but also which antimicrobial treatments are most likely to be effective.
Moving DNA sequencing into clinical practice
Sequencing-based respiratory diagnostics are already beginning to enter clinical practice in some settings.
“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.
Although additional validation will be required before sequencing becomes routine in Australia and elsewhere, she said the technology has considerable potential to transform the diagnosis and management of infectious diseases, including infections associated with CF.
Researchers in Australia are also developing portable sequencing technologies that could potentially be deployed directly in hospitals and even in remote healthcare settings. Such devices could eventually make rapid genomic testing more accessible outside specialized laboratories.
Challenges to widespread adoption
Despite its promise, several barriers currently limit the widespread clinical use of sequencing.
Cost remains an important concern, particularly in healthcare systems and regions with limited laboratory resources. Sequencing also presents technical challenges. Respiratory samples, for example, may contain large amounts of human DNA, making it difficult to distinguish microbial genetic material from DNA belonging to the patient.
Another major challenge is interpretation. While sequencing can generate an enormous amount of information about the microorganisms present in a sample, detecting microbial DNA does not necessarily mean that a particular organism is causing disease. Clinicians therefore need reliable methods for determining which findings are clinically significant and how they should influence treatment decisions.
Standardized laboratory procedures, data-analysis methods, and clinical guidelines will consequently be important before sequencing can be incorporated broadly into routine CF care.
“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.
Understanding how CF treatments reshape the microbiome
Beyond diagnosing infections, sequencing technologies could also help researchers understand how modern CF treatments affect microbial communities in the lungs.
CFTR modulator therapies have substantially improved outcomes and quality of life for many people with CF. However, researchers are still investigating how these treatments alter the airway environment and its microbiome over the long term.
“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.
By tracking these changes, sequencing could provide new insights into the relationship between CF therapies, airway microbial communities, infection risk, and disease progression.
Overall, advances in DNA sequencing are shifting the understanding of CF lung infections away from a model focused primarily on individual pathogens toward one that recognizes the airway as a complex microbial ecosystem. Although further validation, standardization, and cost reductions are needed, these technologies could ultimately support faster diagnosis, more targeted antimicrobial treatment, real-time infection surveillance, and increasingly personalized care for people with cystic fibrosis.
Contact
Jessica A. P. Carlson-Jones
Flinders University – College of Science and Engineering
+61 8 8201 3812