Novel peroxiredoxin defense system from mycobacterium tuberculosis

A method of treating tuberculosis in a subject, said method comprising:

• inhibiting AhpD in the subject under conditions effective to make the pathogen susceptible to antimicrobial reactive nitrogen intermediates or reactive oxygen intermediates.

A method of preventing onset of tuberculosis in a subject infected with Mycobacterium tuberculosis, said method comprising:

• inhibiting dihydrolipoamide dehydrogenase in Mycobacterium tuberculosis in the subject under conditions effective to make the pathogen susceptible to antimicrobial reactive nitrogen intermediates or reactive oxygen intermediates.

A method of treating tuberculosis in a subject, said method comprising:

• inhibiting dihydrolipoamide dehydrogenase in Mycobacterium tuberculosis in the subject under conditions effective to make the pathogen susceptible to antimicrobial reactive nitrogen intermediates or reactive oxygen intermediates.

The method according to claim 23, wherein the dihydrolipoamide dehydrogenase is encoded by an RV0462 gene.

A method of preventing onset of tuberculosis in a subject infected with Mycobacterium tuberculosis, said method comprising:

• inhibiting dihydrolipoamide succinyltransferase in Mycobacterium tuberculosis in the subject under conditions effective to make the pathogen susceptible to antimicrobial reactive nitrogen intermediates or reactive oxygen intermediates.

A method of treating tuberculosis in a subject, said method comprising:

• inhibiting dihydrolipoamide succinyltransferase in Mycobacterium tuberculosis in the subject under conditions effective to make the pathogen susceptible to antimicrobial reactive nitrogen intermediates or reactive oxygen intermediates.

A method of producing an AhpD crystal suitable for X-ray diffraction comprising:

• subjecting a solution of AhpD under conditions effective to grow a crystal of AhpD to a size suitable for X-ray diffraction;
• and
• obtaining an AhpD crystal suitable for X-ray diffraction.

A method for identifying candidate compounds suitable for treatment or prevention of tuberculosis in a subject, said method comprising:

• contacting AhpD with a compound and
• identifying those compounds which bind to the AhpD as candidate compounds suitable for treatment or prevention of tuberculosis in a subject.

A method for identifying candidate compounds suitable for treatment or prevention of tuberculosis in a subject, said method comprising:

• contacting a dihydrolipoamide dehydrogenase in Mycobacterium tuberculosis with a compound and
• identifying those compounds which bind to the dihydrolipoamide dehydrogenase as candidate compounds suitable for treatment or prevention of tuberculosis in a subject.

A method for identifying candidate compounds suitable for treatment or prevention of tuberculosis in a subject, said method comprising:

• contacting a dihydrolipoamide succinyltransferase in Mycobacterium tuberculosis with a compound and
• identifying those compounds which bind to the dihydrolipoamide succinyltransferase as candidate compounds suitable for treatment or prevention of pathogen infection in a subject.

A method for designing a compound suitable for treatment or prevention of tuberculosis in a subject, said method comprising:

• providing a three-dimensional structure of a crystallized AhpD;
• and
• designing a compound having a three-dimensional structure which will bind to one or more molecular surfaces of the AhpD.

A compound suitable for treatment or prevention of tuberculosis in a subject, said compound having a three-dimensional structure which will bind to one or more molecular surfaces of the AhpD having a three dimensional crystal structure defined by the atomic coordinates set forth in FIG. 1.