Exploration of virulence factors, investigation of clinical pathophysiology, and construction of database for cryptococcosis

2013 Fiscal Year Final Research Report

• Project/Area Number: 21390305
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Nagasaki University
• Principal Investigator: KOHNO Shigeru 長崎大学, 医歯(薬)学総合研究科, 教授 (80136647)
• Co-Investigator(Kenkyū-buntansha): 宮崎 義継 国立感染症研究所, 真菌部, 部長 (00311861)
• Co-Investigator(Renkei-kenkyūsha): 泉川 公一 長崎大学, 大学院・医歯薬学総合研究科感染免疫学講座臨床感染症学分野, 教授 (20404212)
• Project Period (FY): 2009-04-01 – 2014-03-31
• Keywords: 感染疫学

Research Abstract

Cryptococcus species isolated from non-HIV patients with cryptococcosis were investigated. However, no apparent relevance was detected between genotype variations (VNI or VNII) and clinical manifestations. Retrospective review of 151 patients with proven pulmonary cryptococcosis.
There were 67 cases (44.4%) in immunocompetent hosts. Eighty-four patients (65.6%) had underlying disease. The most common were diabetes (32.1%), hematologic disease (22.6%), and collagen disease.
Peripherally distributed pulmonary nodules/masses were most commonly seen in both groups. Lesions in the right middle lobe and air bronchogram were significantly more frequent (p = 0.01 and p = 0.05), respectively, in immunocompromised hosts than immunocompetent hosts. Azole-type drugs were mainly selected to treat pulmonary cryptococcosis patients without encephalomeningitis. Mean treatment duration for immunocompetent and immunocompromised patients was 2.87 months and 6.64 months, respectively.

Research Products

• [Journal Article] ER stress response mechanisms in the pathogenic yeast Candida glabrata and their roles in virulence (2014)
  • Author(s): Miyazaki T, Kohno S
  • Journal Title: Virulence Volume: 5(2) Pages: 365-370
• [Journal Article] Multilocus sequence typing of Cryptococcus neoformans in non-HIV associated cryptococcosis in Nagasaki, Japan (2013)
  • Author(s): Mihara T, Izumikawa K, Kakeya H, Ngamskulrungroj P, Umeyama T, Takazono T, Tashiro M, Nakamura S, Imamura Y, Miyazaki T, Ohno H, Yamamoto Y, Yanagihara K, Miyazaki Y, Kohno S
  • Journal Title: Med Mycol Volume: 51(3) Pages: 252-60
• [Journal Article] Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata (2013)
  • Author(s): Miyazaki T, Nakayama H, Nagayoshi Y, Kakeya H, Kohno S
  • Journal Title: PLoS Pathog Volume: 9(1) Pages: e1003160
• [Journal Article] The heme-binding protein Dap1 links iron homeostasis to azole resistance via the P450 protein Erg11 in Candida glabrata (2013)
  • Author(s): Hosogaya N, Miyazaki T, Nagi M, Tanabe K, Minematsu A, Nagayoshi Y, Yamauchi S, Nakamura S, Imamura Y, Izumikawa K, Kakeya H, Yanagihara K, Miyazaki Y, Kugiyama K, Kohno S
  • Journal Title: FEMS Yeast Res Volume: 13(4) Pages: 411-21
• [Journal Article] A case series of chronic necrotizing pulmonary aspergillosis and a new proposal (2013)
  • Author(s): Tashiro T, Izumikawa K, Tashiro M, Morinaga Y, Nakamura S, Imamura Y, Miyazaki T, Kakeya H, Yamamoto Y, Yanagihara K, Hayashi T, Nagayasu T, Kohno S
  • Journal Title: Jpn J Infect Dis Volume: 66(4) Pages: 312-6
• [Journal Article] Necrotizing pneumonia due to femoral osteomyelitis caused by community-acquired methicillin-resistant Staphylococcus aureus (2013)
  • Author(s): Iwanaga N, Fukuda Y, Nakamura S, Imamura Y, Miyazaki T, Izumikawa K, Kakeya H, Yanagihara K, Soda H, Tashiro T, Kohno S
  • Journal Title: Intern Med Volume: 52(13) Pages: 1531-6
• [Journal Article] Azithromycin attenuates lung inflammation in a mouse model of ventilator-associated pneumonia by multidrug-resistant Acinetobacter baumannii (2013)
  • Author(s): Yamada K, Yanagihara K, Kaku N, Harada Y, Migiyama Y, Nagaoka K, Morinaga Y, Nakamura S, Imamura Y, Miyazaki T, Izumikawa K, Kakeya H, Hasegawa H, Mikamo H, Kohno S
  • Journal Title: Antimicrob Agents Chemother Volume: 57(8) Pages: 3883-8
• [Journal Article] Efficacy of AiiM, an N-acylhomoserine lactonase, against Pseudomonas aeruginosa in a mouse model of acute pneumonia (2013)
  • Author(s): Migiyama Y, Kaneko Y, Yanagihara K, Morohoshi T, Morinaga Y, Nakamura S, Miyazaki T, Hasegawa H, Izumikawa K, Kakeya H, Kohrogi H, Kohno S
  • Journal Title: Antimicrob Agents Chemother Volume: 57(8) Pages: 3653-8
• [Journal Article] Toll-like receptor 4 agonistic antibody promotes innate immunity against severe pneumonia induced by coinfection with influenza virus and Streptococcus pneumoniae (2013)
  • Author(s): Tanaka A, Nakamura S, Seki M, Fukudome K, Iwanaga N, Imamura Y, Miyazaki T, Izumikawa K, Kakeya H, Yanagihara K, Kohno S
  • Journal Title: Clin Vaccine Immunol Volume: 20(7) Pages: 977-85
• [Journal Article] In vivo efficacy of daptomycin against methicillin-resistant Staphylococcus aureus in a mouse model of hematogenous pulmonary infection (2013)
  • Author(s): Harada Y, Yanagihara K, Yamada K, Migiyama Y, Nagaoka K, Morinaga Y, Nakamura S, Imamura Y, Hasegawa H, Miyazaki T, Izumikawa K, Kakeya H, Kohno S
  • Journal Title: Antimicrob Agents Chemother Volume: 57(6) Pages: 2841-4
• [Journal Article] Prospective randomized comparison study of piperacillin/tazobactam and meropenem for healthcare-associated pneumonia in Japan (2013)
  • Author(s): Yamamoto Y, Izumikawa K, Morinaga Y, Nakamura S, Kurihara S, Imamura Y, Miyazaki T, Tsukamoto M, Kakeya H, Yanagihara K, Yasuoka A, Kohno S
  • Journal Title: J Infect Chemother Volume: 19(2) Pages: 291-8
• [Journal Article] A case of refractory chronic respiratory tract infection due to Pseudomonas aeruginosa successfully controlled by combination of clarithromycin and azithromycin (2012)
  • Author(s): Yamamoto Y, Izumikawa K, Hosogaya N, Morinaga Y, Nakamura S, Imamura Y, Miyazaki T, Sakamoto N, Ishimatsu Y, Kakeya H, Yanagihara K, Yasuoka A, Kohno S
  • Journal Title: Intern Med Volume: 51 Pages: 1383-6
• [Journal Article] The efficacy and safety of high-dose arbekacin sulfate therapy (once-daily treatment) in patients with MRSA infection (2012)
  • Author(s): Yamamoto Y, Izumikawa K, Hashiguchi K, Fukuda Y, Kobayashi T, Kondo A, Inoue Y, Morinaga Y, Nakamura S, Imamura Y, Miyazaki T, Kakeya H, Yanagihara K, Kohno S
  • Journal Title: J Infect Chemother Volume: 18 Pages: 241-6
• [Journal Article] Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis (2012)
  • Author(s): Izumikawa K, Yamamoto Y, Mihara T, Takazono T, Morinaga Y, Kurihara S, Nakamura S, Imamura Y, Miyazaki T, Nishino T, Tsukamoto M, Kakeya H, Yanagihara K, Mine M, Yasuoka A, Tashiro T, Kohno S
  • Journal Title: Med Mycol Volume: 50 Pages: 811-7
• [Journal Article] Active surveillance of methicillin-resistant Staphylococcus aureus with the BD GeneOhm MRSA^<TM> assay in a respiratory ward in Nagasaki, Japan (2012)
  • Author(s): Izumikawa K, Yamamoto Y, Yanagihara K, Kiya T, Matsuda J, Morinaga Y, Kurihara S, Nakamura S, Imamura Y, Miyazaki T, Nishino T, Tsukamoto M, Kakeya H, Yasuoka A, Tashiro T, Kamihira S, Kohno S
  • Journal Title: Jpn J Infect Dis Volume: 65 Pages: 33-6
• [Journal Article] Correlation between triazole treatment history and susceptibility in clinically isolated Aspergillus fumigatus (2012)
  • Author(s): Tashiro M, Izumikawa K, Hirano K, Ide S, Mihara T, Hosogaya N, Takazono T, Morinaga Y, Nakamura S, Kurihara S, Imamura Y, Miyazaki T, Nishino T, Tsukamoto M, Kakeya H, Yamamoto Y, Yanagihara K, Yasuoka A, Tashiro T, Kohno S
  • Journal Title: Antimicrob Agents Chemother Volume: 56 Pages: 4870-5
• [Journal Article] Antifungal susceptibilities of Aspergillus fumigatus clinical isolates in Nagasaki, Japan (2012)
  • Author(s): Tashiro M, Izumikawa K, Minematsu A, Hirano K, Iwanaga N, Ide S, Mihara T, Hosogaya N, Takazono T, Morinaga Y, Nakamura S, Kurihara S, Imamura Y, Miyazaki T, Nishino T, Tsukamoto M, Kakeya H, Yamamoto Y, Yanagihara K, Yasuoka A, Tashiro T, Kohno S
  • Journal Title: Antimicrob Agents Chemother Volume: 56 Pages: 584-587
• [Presentation] 抗菌化学療法の過去, 未来 (2013)
  • Author(s): 河野茂
  • Organizer: 第83回日本感染症学会西日本地方会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2013-11-06
• [Presentation] 医真菌学の未来を考える (2013)
  • Author(s): 河野茂
  • Organizer: 第57回日本医真菌学会
  • Place of Presentation: 東京
  • Year and Date: 2013-09-27
• [Presentation] 肺炎の克服を目指して (2013)
  • Author(s): 河野茂
  • Organizer: 第110回日本内科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2013-04-13
  • Invited
• [Presentation] 感染症学の未来を創ろう (2012)
  • Author(s): 河野茂
  • Organizer: 第86回日本感染症学会総会
  • Place of Presentation: 長崎
  • Year and Date: 2012-04-25
• [Presentation] 呼吸器感染症診療のこれまでの軌跡と, 未来への展望 (2012)
  • Author(s): 河野茂
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2012-04-21