[Research subject] Analysis of the function of the mycobacterial protein and its contribution to the virulence
We identified a mycobacterial DNA-binding protein, MDP1 (also designated HupB, HLP, LBP, Rv2986c), which is a histone-like protein (A). MDP1 has inhibitory effects on the macromolecular processes, such as DNA replication, RNA, and protein syntheses, which results in suppression of bacterial growth (B). MDP1 is an essential protein in slow growers of mycobacteria but is up-regulated in iron or oxygen-limited condition and participates in the regulation of gene expression in dormancy.
KatG, which is an essential enzyme for activation of isoniazid (INH), is one of the genes regulated by MDP1 and therefore up-regulation of MDP1 confers tolerance to isoniazid (C). Besides regulation of gene expression, MDP1 has iron storage and ferroxidase activities like ferritin, although there is no obvious sequence similarity. Iron is an essential metal for almost all living organisms and ferroxidase activity prevents Fenton reaction, which generates the most aggressive oxygen radical, hydroxyl radical.
Taken together, MDP1 is likely to be involved in growth coordination and prolonging the life of mycobacteria. Immune response to MDP1 is prominent in latent TB and thus this protein is a candidate antigen of diagnosis and vaccine.
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