[S9] Symposium 9
The fascination of mycobacteriology colored by diversity

[S9-2] Inactivation of DNA function by intrinsically disordered histone-like protein in mycobacteria

Akihito Nishiyama¹, Masahiro Shimizu^2,3, Noriyuki Kodera², Anna Savitskaya¹, Yuriko Ozeki¹, Kouta Mayanagi⁴, Takehiro Yamaguchi⁵, Yoshitaka Tateishi¹, Sohkichi Matsumoto¹ (¹Dept. Bacteriol., Sch. Med., Niigata Univ., ²NanoLSI, Kanazawa Univ., ³Div. Quantum Beam Mater. Sci., Inst. Integr. Radiat. Nuc. Sci., Kyoto Univ., ⁴Med. Inst. Bioregulation, Kyushu Univ., ⁵Dept. Pharmacol., Sch. Med., Osaka City Univ.)

Dormancy is the mechanism of survival of living pathogens in the host. Dormant pathogens are tolerant to various stress conditions and antimicrobial chemotherapy. Mycobacteria, major human pathogens, are prone to become dormant persisters. Such latent infection is a major source of mycobacterial diseases, such as tuberculosis. Mycobacterial DNA-binding protein 1 (MDP1) is conserved among all mycobacterial species and essential in Mycobacterium tuberculosis var. tuberculosis. We have identified MDP1 as one of the abundant proteins in hypoxic dormant mycobacteria. MDP1 is a mycobacterial orthologue of histone-like protein HU but possesses a eukaryotic histone tail-like polycationic intrinsically disordered region (IDR) which is rare in bacteria. Recently we have reported that MDP1 induces dormancy phenotypes of mycobacteria, e.g., chromosome compaction, growth suppression, and isoniazid tolerance. Interestingly, IDR is essential for these MDP1 functions, different from other general HUs. However, its strikingly disordered property inhibits the clarification of its detailed molecular mechanism. Here, we summarize our current findings on unique IDR-mediated function of MDP1 and discuss the possible role in dormant mycobacteria.