Completed Infection & Immunity NIHR-supported project Genetics & Molecular Biology

Bloodstream infection diagnosis using long-read metagenomics (Blood-Gen Dx)

Funder NIHR (part of DHSC)
Recipient organisation NIHR Norfolk Clinical Research Facility
NIHR support Recorded as supported by this research centre
Period Jan 2025 — Dec 2025

In plain English

AI plain-English summary

A single blood sample contains too few microbial cells for standard DNA sequencing to reliably detect an infection. Current tests for bloodstream infections are slow and often miss the culprit entirely. Doctors typically rely on blood cultures that take days to grow and fail in up to half of all cases. This delay forces clinicians to prescribe broad-spectrum antibiotics while they wait, contributing to antimicrobial resistance and poor patient outcomes. The problem is that infecting microbes in the blood are present at extremely low abundance—far below what conventional sequencing can pick up. This project aims to solve that bottleneck. The researchers are optimising the earliest steps: how to collect, concentrate, and retain enough microbial DNA from a blood sample to produce a definitive result. If they succeed, a single blood draw could reveal the exact pathogen and its antibiotic resistance profile within hours, not days. The impact would be immediate in hospital settings. Clinicians could switch from guesswork to targeted therapy, reducing unnecessary antibiotic use and improving survival rates for sepsis patients. The work is applied and diagnostic—not fundamental science—and its success depends on solving a practical engineering problem in sample preparation.

View original technical description
It is of critical importance to diagnose bloodstream infections accurately and quickly to ensure optimal management and treatment of patients, and these needs are not often met with current laboratory diagnostic tests on blood. Alternatively, an innovative test is being developed to identify microorganisms in the bloodstream. By performing DNA sequencing directly on blood samples, this new way of testing provides the genetic code of infecting microorganisms, revealing to the medical team the precise cause of the infection and if there are traits related to antibiotic resistance. This research hopes to provide a diagnostic result that, in the future, will help the medical team provide rapid treatments that specifically target the infection. Whereas DNA sequencing works very well for other sample types, such as samples related to respiratory infections, with blood there is often a very small number of microorganisms present. In this study, we seek to answer how do you collect, retain and detect sufficient microorganisms to conclusively determine their presence in blood when these infecting microbes are likely at an exceptionally low abundance? We believe that these issues can be resolved through collaborative research to optimise the critical early steps in obtaining the right blood sample from patients.

Researchers

Matthew Gilmour (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Metagenomics from blood samples to identify causative organism in infective endocarditis: A prospective study to assess Nanopore MinION with host suppression for rapid detection and evaluation of patients with proven infective endocarditis
Investigating the rising incidence of Gram-negative bloodstream infections in England using large linked epidemiology, clinical and genomic datasets
Improving the management of sepsis through rapid pathogen and antibiotic resistance detection in blood
Long-read sequencing to improve diagnostic genetic testing.
Title Direct-from-sample approaches to infection diagnostics using whole genome sequencing, imaging, and protein signatures to diagnose infectious pathogens and determine antimicrobial resistance

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