Diagnosis and monitoring of mycobacterium tuberculosis infection
Disclosed are methods for detecting protein complexes of sigma factors and interacting proteins in a sample containing Mycobacterium tuberculosis . Such methods are useful for the diagnosis and/or monitoring of tuberculosis in a subject. Also disclosed are methods for screening compounds that affect the interaction of one or more sigma factors with one or more interacting proteins.
1. A method for monitoring tuberculosis in a subject comprising:
detecting in a sample from the subject
whether sigma factor σ L of Mycobacterium tuberculosis is bound to the σ L -interacting protein RslA, wherein the presence of unbound σ L is an indicator of active Mycobacterium tuberculosis infection.
2. The method of claim 1 , wherein the status of tuberculosis is active tuberculosis, latent infection or recent infection.
3. The method of claim 1 , wherein the detecting comprises contacting the sample with a solid support conjugated to one or more binding agents having specific binding sites for sigma factor σ L and detecting whether RslA is bound to the sigma factor σ L .
4. The method of claim 3 , wherein the solid support is an antibody array.
5. The method of claim 3 , wherein the one or more binding agents comprise antibodies that have been raised against sigma factor σ L from Mycobacterium tuberculosis.
6. The method of claim 5 , wherein the antibodies are polyclonal antibodies.
7. The method of claim 5 , wherein the antibodies are monoclonal antibodies.
8. The method of claim 1 , further comprising detecting whether one or more additional sigma factors of Mycobacterium tuberculosis are bound to one or more interacting proteins, wherein the one or more additional sigma factors are selected from the group consisting of: σ A , σ B , σ C , σ D , σ E , σ F , σ G , σ H , σ I , σ J , σ K , σ M , and pvdS.
9. The method of claim 1 , wherein the detecting comprises contacting the sample with a solid support conjugated to recombinant sigma factor σ L and detecting whether RslA is bound to the recombinant sigma factor σ L .
10. The method of claim 9 , wherein the solid support is an array of recombinant sigma factor σ L .
11. The method of claim 1 , wherein the detecting comprises immunoprecipitating the sigma factor σ L in the sample and detecting whether RslA is bound to the sigma factor σ L .
12. The method of claim 1 , wherein the sample is a fluid or tissue sample containing Mycobacterium tuberculosis.
13. The method of claim 1 , wherein the sample is from an isolated culture of Mycobacterium tuberculosis from a sample previously obtained from the subject.
14. The method of claim 1 , wherein the sample is a protein extract from a fluid or tissue sample containing Mycobacterium tuberculosis.