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Helmholtz Munich I Daniela Barreto

Detecting Hidden Antibiotic Resistance With Real-Time-Genomics

Featured Publication, Health AI, Pioneer Campus,

A study led by Lara Urban, Principal Investigator at Helmholtz AI and the Pioneer Campus at Helmholtz Munich and TUM Junior Fellow at the Technical University of Munich (TUM), has revealed a novel method for detecting hidden antibiotic resistance, offering new hope for more effective treatments against resistant infections. Published in Nature Communications, this research demonstrates how real-time genomics can quickly and accurately identify antibiotic resistance, even in scenarios where traditional methods fail.

The Threat of Antibiotic Resistance

Antibiotic resistance is one of the most pressing challenges in modern healthcare, threatening to render many of our most potent medicines ineffective. This global health crisis not only compromises patient outcomes but also burdens healthcare systems with increased costs and longer hospital stays. Conventional diagnostic methods rely on culturing and phenotypic testing, which often fail to rapidly and accurately detect resistance, especially for rare or low-abundance mechanisms. The delays in growing cultures and subsequent susceptibility testing can lead to critical delays in administering effective treatment, significantly impacting recovery and survival rates.

Advancing Clinical Diagnostics with Real-Time Genomics

The study showcases major advancements in real-time genomics through nanopore sequencing, providing faster, more detailed analysis of pathogen genomes and resistance profiles than traditional diagnostic tools. The research focused on a severe infection by multi-drug resistant Klebsiella pneumoniae, a common hospital pathogen. Initially treated with Ceftazidime-Avibactam, the patient's condition worsened as the pathogen developed resistance. Traditional diagnostics failed to identify the genetic mechanisms behind this resistance.

Using real-time genomics, the team around first author Ela Sauerborn, PhD student at Helmholtz Munich, discovered complex resistance mechanisms, including a novel plasmid-encoded gene variant. This gene, present in low abundance before treatment, highlights the pathogen's ability to adapt under antibiotic pressure.

 

Real-time genomics involves the rapid analysis and interpretation of genetic data as it is generated, enabling immediate insights into biological processes, disease mechanisms, and evolutionary patterns without delays in data processing. This approach is crucial in fields like healthcare, where timely genetic information can inform treatment decisions and improve patient outcomes.

 

Nanopore sequencing is a cutting-edge technology used to determine the sequence of nucleic acids (DNA or RNA) by passing the molecule through a nanoscale pore. As the molecule moves through the pore, changes in electrical current are detected and interpreted to identify the sequence of bases, providing rapid and portable sequencing capabilities with applications in genomics, medical diagnostics, and environmental studies.

 

Implications for Healthcare

Integrating real-time genomics into clinical practice marks a major shift in managing infectious diseases. Rapid, on-site sequencing enables healthcare providers to quickly tailor treatment strategies to the specific genetic profile of pathogens. This immediate insight into resistance profiles allows clinicians to prescribe the most effective antibiotics, reducing treatment delays and improving patient outcomes while minimizing unnecessary exposure to broad-spectrum antibiotics.

Beyond individual care, real-time genomics-based resistance detection enhances infection control and containment. The rapid turnaround and high resolution of resistance mechanism detection facilitate targeted, immediate containment measures, crucial in high-resistance settings to alter the course of disease outbreaks.

"Our application of nanopore sequencing for hidden antimicrobial resistance detection does not only underscore the technology's potential for rapidly informing clinical management all around the world, but also highlights that it can be more sensitive in detecting rare resistance plasmids than established diagnostics.", says Lara Urban.

 

About the scientist

Dr. Lara Urban, Principal Investigator at Helmholtz AI and the Pioneer Campus at Helmholtz Munich and TUM Junior Fellow at the Technical University of Munich.

Ela Sauerborn, PhD student at Helmholtz Munich and resident clinical microbiologist at the Institute for Medical Microbiology, Immunology and Hygiene at the Technical University of Munich.

Original publication

Sauerborn et al. (2024): Detection of hidden antibiotic resistance through real-time genomics. Nature Communications. DOI: 10.1038/s41467-024-49851-4

Source: Discovering the hidden: Advancing antibiotic resistance detection with real-time genomics | Research Communities by Springer Nature