Alkyl quinolones as biomarkers of pseudomonas aeruginosa infection and uses thereof

Patent metadata

Field	Value
Publication number	US-10139406-B2
Application number	US-201414891242-A
Country	US
Kind code	B2
Filing date	May 13, 2014
Priority date	May 14, 2013
Publication date	Nov 27, 2018
Grant date	Nov 27, 2018

Abstract

A method of determining the P. aeruginosa or related species infection status of a subject comprising: (i) providing a sample of material obtained from the subject; (ii) determining the level of one or more alkyl quinolones or metabolites thereof produced by P. aeruginosa or a related species in the sample

First claim

The invention claimed is:

1. A method of diagnosing and treating a P. aeruginosa or related species infection in a subject suspected of having a P. aeruginosa or related species infection comprising:
(a) providing a sample of blood obtained from the subject;
(b) determining the level of one or more alkyl quinolones produced by P. aeruginosa or a related species in the sample;
(c) comparing the level of the one or more alkyl quinolones in the blood sample with the level of the one or more alkyl quinolones in a reference sample from a subject without the P. aeruginosa or related species infection;
(d) diagnosing the subject with P. aeruginosa or related species infection when an increased level of the one or more alkyl quinolones is detected in the blood sample as compared to the reference sample; and
(e) administering a suitable antibiotic treatment to the diagnosed subject, thereby diagnosing and treating a P. aeruginosa or related species infection in the subject,
wherein the one or more alkyl quinolones is selected from the group consisting of 2-nonyl-4-hydroxyquinoline (HHQ), 2-heptyl-3-hydroxy-4(1H)-quinolone (C7-PQS), 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS), 2-nonyl-4-hydroxyquinoline (NHQ), 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), and 2-nonyl-4-hydroxyquinoline N-oxide (NQNO).

2. The method of claim 1 , further comprising monitoring the effectiveness of the treatment in the subject;
wherein the level of the one or more alkyl quinolones is determined in a second sample obtained from the subject following treatment; and
wherein a reduction in the level of the one or more alkyl quinolones in the second sample indicates that the treatment is effective.

3. The method of claim 1 wherein the level of one or more alkyl quinolones produced by P. aeruginosa or a related species in a sample is determined by mass spectrometry, immunoassays or using a biosensor.

4. The method of claim 1 wherein a species related to P. aeruginosa is a Burkholderia spp.

5. The method of claim 1 wherein the sample of blood is serum.

6. A method of diagnosing and treating a P. aeruginosa or related species infection in a subject suspected of having a P. aeruginosa or related species infection comprising:
(a) providing a sample of urine obtained from the subject;
(b) determining the level of one or more alkyl quinolones produced by P. aeruginosa or a related species in the sample;
(c) comparing the level of the one or more alkyl quinolones in the urine sample with the level of the one or more alkyl quinolones in a reference sample from a subject without the P. aeruginosa or related species infection;
(d) diagnosing the subject with P. aeruginosa or related species infection when an increased level of the one or more alkyl quinolones is detected in the urine sample as compared to the reference sample; and
(e) administering a suitable antibiotic treatment to the diagnosed subject, thereby diagnosing and treating a P. aeruginosa or related species infection in the subject,
wherein the one or more alkyl quinolones is selected from the group consisting of 2-nonyl-4-hydroxyquinoline (HHQ), 2-heptyl-3-hydroxy-4(1H)-quinolone (C7-PQS), 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS), 2-nonyl-4-hydroxyquinoline (NHQ), 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), and 2-nonyl-4-hydroxyquinoline N-oxide (NQNO).

7. The method of claim 1 , wherein the subject has been diagnosed with cystic fibrosis prior to providing the sample.

8. The method of claim 6 , wherein the subject has been diagnosed with cystic fibrosis prior to providing the sample.

9. The method of claim 6 , further comprising monitoring the effectiveness of the treatment in the subject;
wherein the level of the one or more alkyl quinolones is determined in a second sample obtained from the subject following treatment; and
wherein a reduction in the level of the one or more alkyl quinolones in the second sample indicates that the treatment is effective.

10. The method of claim 6 , wherein the level of one or more alkyl quinolones produced by P. aeruginosa or a related species in a sample is determined by mass spectrometry, immunoassays or using a biosensor.

11. The method of claim 6 , wherein a species related to P. aeruginosa is a Burkholderia spp.

Assignees

• Univ Nottingham

Inventors

• Camara Miguel
• Williams Paul
• Barrett David
• Halliday Nigel
• Knox Alan
• Smyth Alan
• Fogarty Andrew
• Barr Helen
• Forrester Doug

Classifications

• C07K16/1214

  Pseudomonadaceae (F) · CPC title

• G01N33/84

  involving inorganic compounds or pH · CPC title

• G01N2469/10

  Detection of antigens from microorganism in sample from host · CPC title

• C07D215/22

  attached in position 2 or 4 · CPC title

• C07H17/02

  Heterocyclic radicals containing only nitrogen as ring hetero atoms · CPC title