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イタノ ナオキ
ITANO NAOKI
板野 直樹 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2009/10 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Mycobacteria Exploit Host Hyaluronan for Efficient Extracellular Replication |
| 執筆形態 | その他 |
| 掲載誌名 | PLOS PATHOGENS |
| 出版社・発行元 | PUBLIC LIBRARY SCIENCE |
| 巻・号・頁 | 5(10),pp.e1000643 |
| 著者・共著者 | Yukio Hirayama,Mamiko Yoshimura,Yuriko Ozeki,Isamu Sugawara,Tadashi Udagawa,Satoru Mizuno,Naoki Itano,Koji Kimata,Aki Tamaru,Hisashi Ogura,Kazuo Kobayashi,Sohkichi Matsumoto |
| 概要 | In spite of the importance of hyaluronan in host protection against infectious organisms in the alveolar spaces, its role in mycobacterial infection is unknown. In a previous study, we found that mycobacteria interact with hyaluronan on lung epithelial cells. Here, we have analyzed the role of hyaluronan after mycobacterial infection was established and found that pathogenic mycobacteria can grow by utilizing hyaluronan as a carbon source. Both mouse and human possess 3 kinds of hyaluronan synthases (HAS), designated HAS1, HAS2, and HAS3. Utilizing individual HAS-transfected cells, we show that HAS1 and HAS3 but not HAS2 support growth of mycobacteria. We found that the major hyaluronan synthase expressed in the lung is HAS1, and that its expression was increased after infection with Mycobacterium tuberculosis. Histochemical analysis demonstrated that hyaluronan profoundly accumulated in the granulomatous legion of the lungs in M. tuberculosis-infected mice and rhesus monkeys that died from tuberculosis. We detected hyaluronidase activity in the lysate of mycobacteria and showed that it was critical for hyaluronan-dependent extracellular growth. Finally, we showed that L-Ascorbic acid 6-hexadecanoate, a hyaluronidase inhibitor, suppressed growth of mycobacteria in vivo. Taken together, our data show that pathogenic mycobacteria exploit an intrinsic host-protective molecule, hyaluronan, to grow in the respiratory tract and demonstrate the potential usefulness of hyaluronidase inhibitors against mycobacterial diseases. |
| DOI | 10.1371/journal.ppat.1000643 |
| ISSN | 1553-7366 |