[ODP-140] 既存薬ライブラリースクリーニングから探る病原性クラミジアが利用する新規細胞内情報伝達系
Recent studies have revealed that Chlamydia trachomatis (Ct) is a risk factor for cervical cancer. We found that Ct activates the PI3K-AKT pathway and adapts to hypoxia, similar to cancer cells. Due to the similarity between Ct-infected cells and cancer cells, the signal transduction pathways utilized by Ct for its growth can be targets for new anticancer agents. However, genetic modification of Ct has not been successful yet. We therefore screened the approved drug libraries through their ability to support or inhibit Ct growth. The approved drug libraries were provided by LTT Bio-Pharma (LTT) (1,241 drugs) and the Center for Drug Discovery Science Education and Research (Hokkaido University) (3,200 drugs). HEp-2 cells were infected with GFP-expressing CtL2 (434/Bu) with MOI5, and cultured at 21%O2 or 2%O2 in the presence of approved drugs for 48 h. The success or failure of Ct growth was judged using an inclusion body formation assay. As a result, 13 drugs from the libraries (excluding antibacterial agents) were identified to inhibit Ct growth. From the comparison with the KEGG database, dopaminergic synapse (hsa04080), aldosterone regulation/sodium reabsorption (hsa04960), and others were identified as potential signal transduction pathways affected by these hit drugs.
(Non-member collaborators: Zhang Xinyue, Mutuko Otoguro, Manabu Nagao, Yuichi Takizawa)