Detection of bacterial infections

Abstract

The present invention relates to methods of detecting an infection in a subject based on the relative abundance of target molecules indicative of the expression of at least the gene pair DUSP1 and IFI27. In particular, the invention relates to a method of distinguishing between a bacterial infection or a non-bacterial infection in a subject, especially between bacterial and non-bacterial lower respiratory system infections using the gene pair. Further, the invention provides the medical use of therapeutic agents in the treatment of a bacterial or non-bacterial infection in a subject identified as having such an infection through use of a method of the invention, and monitoring the therapeutic effectiveness.

1 - 25 . (canceled) 
     
     
         26 . A method of detecting and optionally treating a bacterial infection in a subject, the method comprising:
 (a) assaying a body fluid sample obtained from the subject to determine expression of at least the gene pair ELANE and IFI27 relative to each other; and   (b) determining the presence of the bacterial infection in the subject based on the presence of the expression of at least the gene pair ELANE and IFI27 relative to each other; and optionally,   (c) treating the subject having the bacterial infection by administering a therapeutically effective amount of an antibacterial agent.   
     
     
         27 . The method of  claim 26 , comprising treating the subject having the bacterial infection by administering a therapeutically effective amount of an antibacterial agent. 
     
     
         28 . The method of  claim 26 , wherein the bacterial infection is caused by a bacterium selected from the group consisting of:  Streptococcus pneumoniae; Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae; Legionella pneumonia, Escherichia coli,  and  Haemophilus influenza.    
     
     
         29 . The method of  claim 26 , wherein the bacterial infection is a lower respiratory system infection and is caused by one or more pathogens selected from the group consisting of:  Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Pseudomonas aeruginosa, Bordatella pertussis, Neisseria meningitidis, Coxiella burnetiid, Corynebacterium, Klebsiella pneumoniae; Legionella pneumonia, Escherichia coli, Haemophilus influenza, Moraxella catarrhalis, Mycoplasma pneumoniae, Acinetobacter baumannii, Chlamydophila  ( Chlamydia )  pneumoniae, Bordatella parapertussis, Neisseria gonorrhoeae, Campylobacter jejuni, Listeria monocytogenes, Mycobacteria tuberculosis  and nontuberculous mycobacteria. 
     
     
         30 . The method of  claim 29 , wherein the lower respiratory system infection is pneumonia and is caused by one or more pathogens selected from the group consisting of:  Chlamydia pneumoniae, Escherichia coli, Haemophilus influenza, Klebsiella pneumoniae, Legionella pneumonia, Moraxella catarrhalis, Mycoplasma pneumoniae, Neisseria meningitides, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus agalactiae, and    Streptococcus pneumoniae.    
     
     
         31 . The method of  claim 26 , wherein the bacterial infection is a bacterial infection syndrome, selected from the group consisting of
 i) sepsis caused by a bacterium selected from the group consisting of:  Acinetobacter baumannii, Staphylococcus epidermidis, Staphylococcus saprophyticus,  and  Streptococcus pyogenes,  and   ii) bacterial gastroenteritis.   
     
     
         32 . The method of  claim 26 , wherein the body fluid sample is selected from the group consisting of: a whole blood sample; a blood plasma sample; a serum sample; a cerebrospinal fluid (CSF) sample; and a synovial fluid sample. 
     
     
         33 . The method of  claim 26 , wherein step (a) comprises determining the expression of at least one further gene pair relative to each other. 
     
     
         34 . The method of  claim 33 , wherein the at least one further gene pair is selected from the group: DUSP1 and IFI27; DUSP1 and SIGLEC1; DUSP1 and IFI44L; ELANE and SIGLEC1; ELANE and IFI44L; CTSG and IFI44L; ELANE and S1PR5; CTSG and S1PR5; GRK6 and TXLNA; APMAP and KMT2A; DUSP1 and HP1BP3; FLOT1 and NMT1; APMAP and HUWE1; ELANE and SIGLEC1; and DUSP1 and NMT1. 
     
     
         35 . The method of  claim 33 , wherein the at least one further gene pair is selected from the group: DUSP1 and SIGLEC1; DUSP1 and IFI44L; ELANE and SIGLEC1; and ELANE and IFI44L. 
     
     
         36 . The method of  claim 26 , wherein step (b) comprises calculating the relative abundance ratio of the one or more gene pair(s). 
     
     
         37 . The method of  claim 36 , wherein step (b) further comprises comparing the relative abundance ratio of the one or more gene pair(s) to a predetermined threshold value. 
     
     
         38 . The method of  claim 37 , wherein step (b) further comprises determining whether the relative abundance ratio of the one or more gene pair(s) under consideration exceeds a predetermined threshold value, wherein the predetermined threshold value is 1.18. 
     
     
         39 . The method of  claim 26 , wherein assaying the body fluid sample comprises using a technique selected from the group consisting of RT-PCR, real-time PCR, Northern blot, RNA sequencing (RNA-seq) and RNA microarray. 
     
     
         40 . The method of  claim 26 , wherein assaying the body fluid sample comprises using a technique selected from the group consisting of enzyme-linked immunosorbent assay (ELISA), radioimmunoassay, immunoprecipitation, Western blot and mass spectrometry.