Alpha-Crystalline Protein Expression & Inducing of the Nonreplicating Persistence States of Mycobacterium Tuberculosis

Latent tuberculosis infection (LTBI) is caused by mycobacterium tuberculosis in a state of non-replicating persistence (NRP). Recent evidence suggests that some very specific adaptations to oxygen depletion occur that MTB undergoes to hypoxic RNP state. In this study the modified slowly stirred, limited Head Space Ratio (0.5HSR) method was used to investigate the physiological response of MTB to different oxygen tension levels. For setting up the various NRP stages 100 susceptible & drugs resistant clinically isolated strains of MTB were cultivated in Dubos Albomin Tween medium via hypoxically, slow stirring 0.5 HSR method and the effects of isoniazid, rifampin, pyrazinamide. ciprofloxacin & metronidazole against MTB were examined during NRP-1 and NRP-2 stages. The α-crystalline protein was detected during NRP-1 stage of the MTB cultures via performance of the suitable procedures for pellet preparation, washing and cell disruption and SDS-PAGE technique. NRP-1, NRP-2 stages of MTB subjected to be test documentary were seen. The first three of the four drugs mentioned above affected the MTB at actively replicating period and the rifampin effect was continued slightly during NRP-1 stage. Meteronidazole was affected the MTB at anaerobic NRP-2 stage. α- crystalline protein was detected at NRP -1 stage but do not detect at aerated cultures. Induction of the α-crystalline protein during hypoxic shift-down of MTB metabolism, its function as a chaperone, suggests a critical role for this protein in the ability of MTB to persist without replicating in the hostile regions of the host''s tissues. Therefore, understanding of the mechanisms of induction of factors associated with the hypoxic condition of tubercle bacilli that should be contribute to the development of strategies for identification of the new drugs targets and preventing the persistence states in human lesions must be critical for affective TB control programs.