Marker of Pseudomonas infection in urine/blood and saliva

Description:

Rapid and reliable diagnosis of Pseudomonas aeruginosa infection

Summary

We have found and characterised novel biomarkers which accurately report on the Pseudomonas aeruginosa infection status of individuals with compromised lung function. The biomarkers offer the promise of being able to accurately and quickly determine whether infection is present so that therapies can be tailored for individuals, applied quickly and effectively and so that infection can be easily monitored on an ongoing basis. The markers also provide an effective system for epidemiological studies.  

The markers we have identified are quorum sensing signals and their metabolites originating from a large number of clinical Pseudomonas aeruginosa infections in cystic fibrosis patients. Samples are taken non-invasively so there is no challenge in being able to access informative samples. Analysis is currently performed using mass spectroscopy but could be adapted to other technologies such as ELISA, etc. We are currently developing simple highly sensitive biosensor tests which could in future be developed into diagnostic kits.  

We seek a company to work with us to develop these diagnostic assays for clinical use.

Background & Key Benefits

The bacterium Pseudomonas aeruginosa (PA) infects the lungs of patients who are already suffering from chronic diseases such as cystic fibrosis (CF), COPD and bronchiestasis. Infection tends to persist and is a key factor in accelerating disease progression which clearly has negative implications for the patient as well as increasing costs.

Routine diagnosis of PA infection is via standard bacterial culture which is time-consuming and does not permit appropriate treatment of exacerbations. Many patients are unable to provide the sputum samples needed for analysis. A new approach is urgently needed to prevent accelerated declines in lung function and subsequent clinical deterioration. Other techniques such as PCR have been tried but no reliable DNA markers were found. At Nottingham, we have been capitalising on our world leading expertise in the molecular microbiology of PA and strong clinical cystic fibrosis research to identify novel biomarkers of P. aeruginosa infection.

The Market

By way of example, the annual cost of care for each CF patient exceeds £3600 in childhood, equivalent to CF treatment costs of £28million per year in the UK. In fact much of this cost is associated with controlling PA infection. COPD costs the NHS £982 million per year. A significant part of this cost is associated with PA infection which is found in 31% of patients and which is associated with disease exacerbation, often leading to hospitalisation. The ability to be more responsive and manage PA infections effectively brings patient benefit and major cost savings.

Technical Information

Professors Miguel Cámara and Dave Barrett together with close colleagues lead a team which is carrying out clinical research for a diagnostic test for Pseudomonas aeruginosa. Through a study involving nearly 300 cystic fibrosis patients including both paediatric and adult populations we have demonstrated, using mass-spectrometry analysis a correlation between the presence of Pseudomonas aeruginosa in the lungs of these patients and the presence of quorum sensing signal molecules (QSSMs) and their metabolic products. These bio-markers were not only found reliably and routinely in sputum but in several different body fluids including urine which will facilitate future sampling. The QSSMs were not present in samples from healthy individuals. This has confirmed the usefulness of the identification of these molecules as biomarkers of PA infections which could potentially be extrapolated to other infections caused by PA such as wound infections and a number of post-surgery infections.

We are currently designing fast detection mass-spectrometry assays with minimal sample processing and highly sensitive biosensors for the detection of QSSM from biological samples which could routinely be used in the clinic in the future.

Figure 1. Detection of QSSM from biological samples using a luminescent based biosensors A. Overlay of a thin layer chromatogram with biosensor. B. Microtiter-plate based bioluminescent assay mixing sample with biosensor.

Further details about some the technologies can be found in the following publications.

[1] Fletcher MP, Diggle SP, Crusz SA, Chhabra SR, Camara M & Williams P (2007) A dual biosensor for 2-alkyl-4-quinolone quorum-sensing signal molecules. Environmental Microbiology 9: 2683-2693.
[2] Middleton B, Rodgers HC, Camara M, Knox AJ, Williams P & Hardman A (2002) Direct detection of N-acylhomoserine lactones in cystic fibrosis sputum. Fems Microbiology Letters 207: 1-7.
[3] Ortori CA, Dubern JF, Chhabra SR, Camara M, Hardie K, Williams P & Barrett DA Simultaneous quantitative profiling of N-acyl-L-homoserine lactone and 2-alkyl-4(1H)-quinolone families of quorum-sensing signaling molecules using LC-MS/MS. Anal Bioanal Chem 399: 839-850.

IP Status

The University filed a UK priority patent application filing (GB 1117881.1) ahead of publications on the technology by the academic team.

We wish to engage with medical diagnostics companies to work with us and / or to licence the patent-protected biomarker technology and develop the diagnostic for the clinic.

Patent Information:
For Information, Contact:
Caroline Sykes
IP Commercialisation Manager - Healthcare
The University of Nottingham
0115 82 30042
Caroline.Sykes@nottingham.ac.uk
Inventors:
Miguel Camara-Garcia
Andrew Fogarty
David Barrett
Paul Williams
Nigel Halliday
Keywords:
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