[ODP19] 4. 遺伝・ゲノミクス・バイオテクノロジー-d. 遺伝子組換え・解析技術・バイオテクノロジー・合成生物学

[ODP-093] 抗酸菌のプロテアーゼclpは有望な新規抗結核薬標的である

山口 雄大^1,2，寒川 訓明¹，尾関 百合子³，松本 壮吉³，冨田 修平¹ (¹大阪市立大・医・分子病態薬理，²国立感染症研究所・細菌第一部，³新潟大・医・細菌)

Background: Tuberculosis (TB), caused by the bacillus Mycobacterium tuberculosis (Mtb), is the world’s leading infections disease. Because of increasing emergence of drug-resistant Mtb, development of a novel anti-TB drug is required. Bacterial proteases are maintaining proteostasis and essential for bacterial survival. Here, we investigated whether bacterial proteases are feasible for targets of anti-TB drugs.
Methods and Results: Inducible knockdown strains of proteases (clp, ftsH or htrA) in Mycobacterium smegmatis mc2-155 were created by using clustered regularly interspaced short palindromic repeats interference (CRISPRi). Although gene knockdown of the proteases did not suppress bacterial growth, knockdown of htrA conferred resistance to isoniazid and knockdown of clp increased the susceptibility against isoniazid and rifampicin, traditional anti-TB drugs. Furthermore, checkerboard assay revealed the synergistic effect between cyclomarin A, a novel clp inhibitor, and anti-TB drugs.
Conclusions: Clp is a promising drug target for development of a novel anti-TB drug.