[S9] シンポジウム9
多様性で彩る抗酸菌研究の魅力

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

西山 晃史¹，清水 将裕^2,3，古寺 哲幸²，Anna Savitskaya¹，尾関 百合子¹，真柳 浩太⁴，山口 雄大⁵，立石 善隆¹，松本 壮吉¹ (¹新潟大院・医歯学総合・細菌，²金沢大・ナノ生命科学研，³京都大・複合原子力科学研，⁴九州大・生体防御医学研，⁵大阪市大院・医・分子病態薬理)

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.