[WS8] Molecular basis of hypoxic environment and associated diseases (cancer, infectious diseases)

[WS8-4] Mycobacterial DNA-binding protein 1, a major protein in hypoxic dormant mycobacteria

○Akihito Nishiyama¹, Noriyuki Kodera², Masahiro Shimizu³, Anna Savitskaya¹, Shymaa Enany¹, Kouta Mayanagi⁴, Takehiro Yamaguchi⁵, Yuriko Ozeki¹, Yoshitaka Tateishi¹, Sohkichi Matsumoto¹ (¹Dept. Bacteriol., Sch. Med., Niigata Univ., ²NanoLSI, Kanazawa Univ., ³KURNA, Kyoto Univ., ⁴Med. Inst. Bioregulation, Kyushu Univ., ⁵Dept. Pharmacol., Med. Sch., Osaka City Univ.)

Mycobacteria can survive long periods in the host as a dormant state. As for tuberculosis, such latent infection is a major source of infection. Mycobacterial DNA-binding protein 1 (MDP1), which is conserved among all mycobacterial species and essential in slow growers such as Mycobacterium tuberculosis var. tuberculosis, was identified as one of the most abundant proteins in hypoxic dormant mycobacteria, suggesting a significant role in the growth regulation and adaptation. MDP1 is a mycobacterial orthologue of bacterial histone-like protein HU, but possesses eukaryotic histone H1-like intrinsically disordered region (IDR) that is not seen in most of other HUs. We recently showed that MDP1 plays a role in chromosome condensation and suppresses multiple cellular functions such as replication and metabolism in the stationary phase, which is important in the long-term survival of mycobacteria. Interestingly, unlike IDR-deficient general HUs, IDR is required to express such MDP1 functions (e.g., chromosome organization, growth/replication, drug tolerance). These data suggest the pivotal role of mycobacteria-specific IDR in MDP1 functions. Here, we summarize our current findings on unique IDR-dependent functions of MDP1 in mycobacteria including the current update of functional study.