Methods for detecting and treating Mycobacterium-related diseases including reducing Mycobacterial virulence, reducing RV3133c dimerization, and treating a subject with a Mycobacterial infection using identified compounds are disclosed. Examples of compounds useful in the treatment of Mycobacterium-related diseases include N-(4-[(acetylamino)sulfonyl]phenyl)-3-phenylpropanamide 1-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-(2-imino-3-methyl-2,3-dihydro-1H-benzimidazol-1yl)ethanone hydrochloride and 1-(1,3-benzoxazol-2-yl)-3-({4-[(2-hydroxyethyl)sulfonyl]phenyl}amino)acrylaldehyde. Further disclosed are methods for identifying agents that interact with a polypeptide in a Mycobacterium cell.