2021/04/08 更新

写真a

ミズノ タマキ
水野 環
MIZUNO Tamaki
所属
医歯薬学総合研究科
外部リンク

学位

  • 博士(薬学) ( 岡山大学 )

研究キーワード

  • プロテアーゼ

  • 細菌毒素

  • 環境微生物

  • 病原細菌

  • VBNC

  • 下痢症

研究分野

  • ライフサイエンス / 薬系衛生、生物化学

  • ライフサイエンス / 細菌学

  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含まない

  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含む

  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含む

  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含まない

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学歴

  • 岡山大学   大学院医歯薬学総合研究科   創薬生命科学専攻(博士後期課程)

    2007年4月 - 2010年3月

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  • 岡山大学   大学院医歯薬学総合研究科   創薬生命科学専攻(博士前期課程)

    2005年4月 - 2007年3月

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  • 岡山大学   薬学部   総合薬学科

    2001年4月 - 2005年3月

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経歴

  • 岡山大学   医歯薬学総合研究科   助教

    2015年12月 - 現在

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  • 岡山大学   インド感染症共同研究センター   特任助教

    2011年12月 - 2015年11月

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  • 岡山大学   医歯薬学総合研究科   博士研究員

    2010年5月 - 2011年11月

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所属学協会

 

論文

  • Comparative genome analysis of VSP-II and SNPs reveals heterogenic variation in contemporary strains of Vibrio cholerae O1 isolated from cholera patients in Kolkata, India 査読

    Daisuke Imamura, Masatomo Morita, Tsuyoshi Sekizuka, Tamaki Mizuno, Taichiro Takemura, Tetsu Yamashiro, Goutam Chowdhury, Gururaja P. Pazhani, Asish K. Mukhopadhyay, Thandavarayan Ramamurthy, Shin-Ichi Miyoshi, Makoto Kuroda, Sumio Shinoda, Makoto Ohnishi

    PLoS Neglected Tropical Diseases   11 ( 2 )   e0005386   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science  

    Cholera is an acute diarrheal disease and a major public health problem in many developing countries in Asia, Africa, and Latin America. Since the Bay of Bengal is considered the epicenter for the seventh cholera pandemic, it is important to understand the genetic dynamism of Vibrio cholerae from Kolkata, as a representative of the Bengal region. We analyzed whole genome sequence data of V. cholerae O1 isolated from cholera patients in Kolkata, India, from 2007 to 2014 and identified the heterogeneous genomic region in these strains. In addition, we carried out a phylogenetic analysis based on the whole genome single nucleotide polymorphisms to determine the genetic lineage of strains in Kolkata. This analysis revealed the heterogeneity of the Vibrio seventh pandemic island (VSP)-II in Kolkata strains. The ctxB genotype was also heterogeneous and was highly related to VSP-II types. In addition, phylogenetic analysis revealed the shifts in predominant strains in Kolkata. Two distinct lineages, 1 and 2, were found between 2007 and 2010. However, the proportion changed markedly in 2010 and lineage 2 strains were predominant thereafter. Lineage 2 can be divided into four sublineages, I, II, III and IV. The results of this study indicate that lineages 1 and 2-I were concurrently prevalent between 2007 and 2009, and lineage 2-III observed in 2010, followed by the predominance of lineage 2-IV in 2011 and continued until 2014. Our findings demonstrate that the epidemic of cholera in Kolkata was caused by several distinct strains that have been constantly changing within the genetic lineages of V. cholerae O1 in recent years.

    DOI: 10.1371/journal.pntd.0005386

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  • International Collaborative Research on Infectious Diseases by Japanese Universities and Institutes in Asia and Africa, with a Special Emphasis on J-GRID 査読

    Sumio Shinoda, Daisuke Imamura, Tamaki Mizuno, Shin-Ichi Miyoshi, Thandavrayan Ramamurthy

    BIOCONTROL SCIENCE   20 ( 2 )   77 - 89   2015年6月

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    記述言語:英語   出版者・発行元:SOC ANTIBACTERIAL & ANTIFUNGAL AGENTS, JAPAN  

    In developed countries including Japan, malignant tumor (cancer), heart disease and cerebral apoplexy are major causes of death, but infectious diseases are still responsible for a high number of deaths in developing countries, especially among children aged less than 5 years. World Health Statistics published by WHO reports a high percentage of mortality from infectious diseases in children, and many of these diseases may be subject to transmission across borders and could possibly invade Japan.
    Given this situation, the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan initiated Phase I of the Program of Founding Research Centers for Emerging and Reemerging Infectious Disease, which ran from FY 2005 to 2009, and involved 8 Japanese universities and 2 research centers. The program was established for the following purposes: 1) creation of a domestic research structure to promote the accumulation of fundamental knowledge about infectious diseases, 2) establishment of 13 overseas research collaboration centers in 8 countries at high risk of emerging and reemerging infections and at which Japanese researchers are stationed and conduct research in partnership with overseas instructors, 3) development of a network among domestic and overseas research centers, and 4) development of human resources.
    The program was controlled under MEXT and managed by the RIKEN Center of Research Network for Infectious Diseases (Riken CRNID). Phase II of the program was set up as the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID), and has been running in FY 2010-2014.
    Phase III will start in April 2015, and will be organized by the newly established Japanese governmental organization "Japan Agency for Medical Research and Development (AMED)'', the so-called Japanese style NIH.
    The Collaborative Research Center of Okayama University for Infectious Diseases in India (CRCOUI) was started up in 2007 at the National Institute of Cholera and Enteric Disease, Kolkata, India. Major projects of CRCOUI are concerned with diarrheal diseases such as, 1) active surveillance of diarrhea! patients, 2) development of dysentery vaccines, 3) viable but nonculturable (VBNC) Vibrio cholerae, and 4) pathogenic mechanisms of various diarrhogenic microorganisms.
    This review article outlines project of J-GRID and CRCOUI which the authors carried out collaboratively with NICED staff members.

    DOI: 10.4265/bio.20.77

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  • Stepwise changes in viable but nonculturable Vibrio cholerae cells 査読

    Daisuke Imamura, Tamaki Mizuno, Shin-ichi Miyoshi, Sumio Shinoda

    MICROBIOLOGY AND IMMUNOLOGY   59 ( 5 )   305 - 310   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Many bacterial species are known to become viable but nonculturable (VBNC) under conditions that are unsuitable for growth. In this study, the requirements for resuscitation of VBNC-state Vibrio cholerae cells were found to change over time. Although VBNC cells could initially be converted to culturable by treatment with catalase or HT-29 cell extract, they subsequently entered a state that was not convertible to culturable by these factors. However, fluorescence microscopy revealed the presence of live cells in this state, from which VBNC cells were resuscitated by co-cultivation with HT-29 human colon adenocarcinoma cells. Ultimately, all cells entered a state from which they could not be resuscitated, even by co-cultivation with HT-29. These characteristic changes in VBNC-state cells were a common feature of strains in both V. cholerae O1 and O139 serogroups. Thus, the VBNC state of V. cholerae is not a single property but continues to change over time.

    DOI: 10.1111/1348-0421.12246

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  • Defensive Effects of Human Intestinal Antimicrobial Peptides against Infectious Diseases Caused by Vibrio mimicus and V. vulnificus 査読

    Shin-Ichi Miyoshi, Hiroto Ikehara, Mika Kumagai, Tamaki Mizuno, Tomoka Kawase, Yoko Maehara

    BIOCONTROL SCIENCE   19 ( 4 )   199 - 203   2014年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC ANTIBACTERIAL & ANTIFUNGAL AGENTS, JAPAN  

    Of human pathogenic Vibrio species, V mimicus causes gastroenteritis whereas V vulnificus causes fatal septicemia after consumption of contaminated seafood. These two pathogens produce hemolytic toxins termed V mimicus hemolysin (VMH) and V vulnificus hemolysin (VVH), respectively. These toxins elicit the cytolysis of various eukaryotic cells, as well as erythrocytes. The human intestine secretes cationic antimicrobial peptides (AMPs) to prevent infectious diseases. Paneth cells in the small intestine secrete a-defensin 5 (HD-5) and epithelial cells in the large intestine produce LL-37. In the present study, we examined the bactericidal activities of AMPs against V mimicus and V vulnificus. Although HD-5 showed no bactericidal activity, LL-37 revealed significant activity against both Vibrio species, suggesting that neither V mimicus nor V vulnificus can multiply in the large intestine. We also tested whether AMPs had the ability to inactivate the hemolytic toxins. Only HD-5 was found to inactivate VMH, but not VVH, in a dose-dependent manner through the direct binding to VMH. Therefore, it is considered that V mimicus cannot penetrate the small intestinal epithelium because the cytolytic action of VMH is inactivated by HD-5.

    DOI: 10.4265/bio.19.199

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  • A novel extracellular protease of Vibrio mimicus that mediates maturation of an endogenous hemolysin 査読

    Tamaki Mizuno, Ayako Nanko, Yoko Maehara, Sumio Shinoda, Shin-Ichi Miyoshi

    MICROBIOLOGY AND IMMUNOLOGY   58 ( 9 )   503 - 512   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Vibrio mimicus, a human pathogen that causes gastroenteritis, produces an enterotoxic hemolysin as a virulence factor. The hemolysin is secreted extracellularly as an inactive protoxin and converted to a mature toxin through removal of the N-terminal propeptide, which comprises 151 amino acid residues. In this study, a novel protease having the trypsin-like substrate specificity was purified from the bacterial culture supernatant. The N-terminal amino acid sequence of the purified protein was identical with putative trypsin VMD27150 of V. mimicus strain VM573. The purified protease was found to cause maturation of the protoxin by cleavage of the Arg(151)Ser(152) bond. Deletion of the protease gene resulted in increased amounts of the protoxin in the culture supernatant. In addition, expression of the hemolysin and protease genes was detected during the logarithmic growth phase. These findings indicate that the protease purified may mediate maturation of the hemolysin.

    DOI: 10.1111/1348-0421.12177

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  • Isolation of viable but nonculturable Vibrio cholerae O1 from environmental water samples in Kolkata, India, in a culturable state 査読

    Mitsutoshi Senoh, Jayeeta Ghosh-Banerjee, Tamaki Mizuno, Sumio Shinoda, Shin-ichi Miyoshi, Takashi Hamabata, G. Balakrish Nair, Yoshifumi Takeda

    MICROBIOLOGYOPEN   3 ( 2 )   239 - 246   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Previously, we reported that viable but nonculturable (VBNC) Vibrio cholerae was converted into a culturable state by coculture with several eukaryotic cell lines including HT-29 cells. In this study, we found that a factor converting VBNC V. cholerae into a culturable state (FCVC) existed in cell extracts of eukaryotic cells. FCVC was nondialyzable, proteinase K-sensitive, and stable to heating at <60 degrees C for 5 min. We prepared thiosulfate citrate bile salts sucrose (TCBS) plates with FCVC (F-TCBS plates). After confirming that VBNC V. cholerae O1 and O139 formed typical yellow colonies on F-TCBS plates, we tried to isolate cholera toxin gene-positive VBNC V. cholerae from environmental water samples collected in urban slum areas of Kolkata, India and succeeded in isolating V. cholerae O1 El Tor variant strains harboring a gene for the cholera toxin. The possible importance of VBNC V. cholerae O1 as a source of cholera outbreaks is discussed.

    DOI: 10.1002/mbo3.164

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  • Ecological Study of Pathogenic Vibrios in Aquatic Environments 査読

    Sumio Shinoda, Yuki Furumai, Sei-Ichi Katayama, Tamaki Mizuno, Shin-Ichi Miyoshi

    BIOCONTROL SCIENCE   18 ( 1 )   53 - 58   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC ANTIBACTERIAL & ANTIFUNGAL AGENTS, JAPAN  

    An ecological study of pathogenic vibrios in aquatic environments of Okayama was carried out. The number of Vibrio parahaemolyticus detected in the sea area was comparatively smaler than that found in the survey of about two decades ago. Various reasons for the decrease in the case of food poisoning by V. parahaemolyticus have been suggested but the lower number of the vibrio in aquatic environments may be one explanation. Although the number of V. vulnificus was also not as large, most of the isolates possessed the pathogenic genes, vvp and vvh, suggesting the potential for fatal pathogenicity to patients having underlying diseases. As for V. cholerae, some non-O1/non-O139 serovar isolates were detected in a fresh water area, and many of them had hlyA, the gene for hemolysin which acts as a pathogenic factor in sporadic cases of diarrhea. Thus, the total number of pathogenic vibrios detected was not of concern. However, the marine products of these areas are shipped in wide area and are for general consumption. Therefore, it is necessary to continue to survey pathogenic vibrios in aquatic environments in order to ensure food hygiene.

    DOI: 10.4265/bio.18.53

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  • An extracellular serine protease produced by Vibrio vulnificus NCIMB 2137, a metalloprotease-gene negative strain isolated from a diseased eel 査読

    Shin-ichi Miyoshi, Jiyou Wang, Keizo Katoh, Mitsutoshi Senoh, Tamaki Mizuno, Yoko Maehara

    WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY   28 ( 4 )   1633 - 1639   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Vibrio vulnificus is a ubiquitous estuarine microorganism but causes fatal systemic infections in immunocompromised humans, cultured eels or shrimps. An extracellular metalloprotease VVP/VvpE has been reported to be a potential virulence factor of the bacterium; however, a few strains isolated from a diseased eel or shrimp were recently found to produce a serine protease termed VvsA, but not VVP/VvpE. In the present study, we found that these strains had lost the 80 kb genomic region including the gene encoding VVP/VvpE. We also purified VvsA from the culture supernatant through ammonium sulfate fractionation, gel filtration and ion-exchange column chromatography, and the enzyme was demonstrated to be a chymotrypsin-like protease, as well as those from some vibrios. The gene vvsA was shown to constitute an operon with a downstream gene vvsB, and several Vibrio species were found to have orthologues of vvsAB. These findings indicate that the genes vvp/vvpE and vvsAB might be mobile genetic elements.

    DOI: 10.1007/s11274-011-0969-y

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  • Inactivation of Vibrio vulnificus hemolysin through mutation of the N- or C-terminus of the lectin-like domain 査読

    Shin-ichi Miyoshi, Yuki Abe, Mitsutoshi Senoh, Tamaki Mizuno, Yoko Maehara, Hiroshi Nakao

    TOXICON   57 ( 6 )   904 - 908   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Vibrio vulnificus is an etiological agent causing serious systemic infections in the immu-nocompromised humans or cultured eels. This species commonly produces a hemolytic toxin consisting of the cytolysin domain and the lectin-like domain. For hemolysis, the lectin-like domain specifically binds to cholesterol in the erythrocyte membrane, and to form a hollow oligomer, the toxin is subsequently assembled on the membrane. The cytolysin domain is essential for the process to form the oligomer. Three-dimensional structure model revealed that two domains connected linearly and the C-terminus was located near to the joint of the domains. Insertion of amino acid residues between two domains was found to cause inactivation of the toxin. In the C-terminus, deletion, substitution or addition of an amino acid residue also elicited reduction of the activity. However, the cholesterol-binding ability was not affected by the mutations. These results suggest that mutation of the C- or N-terminus of the lectin-like domain may result in blockage of the toxin assembly. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.toxicon.2011.03.013

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  • Defensive Effects of Human Antimicrobial Peptide alpha-Defensins against Enterococcus faecalis 査読

    Shin-ichi Miyoshi, Kenta Koyama, Tamaki Mizuno, Minoru Kashihara, Yoko Maehara, Hiroshi Nakao

    JOURNAL OF HEALTH SCIENCE   56 ( 5 )   618 - 622   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Cationic and amphiphilic antimicrobial peptides (AMPs) such as alpha-defensins and cathelicidins are factors related to innate immunity. In the present study, we examined the protective effects of two AMPs, human neutrophil peptide-3 and alpha-defensin-5, against the opportunistic pathogen Enterococcus faecalis (E. faecalis). The alpha-defensins had dose-dependent bactericidal activity, whereas they showed no synergistic effect on the antimicrobial actions of antibiotics. Although AMPs often neutralize bacterial bioactive products, neither alpha-defensin reduced the proteolytic activity of GelE, a toxic protease from E. faecalis. On the other hand, the alpha-defensins were found to be fairly stable even in the presence of excess amounts of GelE. These results indicate that alpha-defensins may be defensive factors against E. faecalis in humans.

    DOI: 10.1248/jhs.56.618

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  • Modulation of Vibrio mimicus hemolysin through limited proteolysis by an endogenous metalloprotease 査読

    Tamaki Mizuno, Syed Z. Sultan, Yoshimi Kaneko, Tomonaga Yoshimura, Yoko Maehara, Hiroshi Nakao, Tomofusa Tsuchiya, Sumio Shinoda, Shin-ichi Miyoshi

    FEBS JOURNAL   276 ( 3 )   825 - 834   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Vibrio mimicus is a causative agent of human gastroenteritis and food poisoning, and this species produces an enterotoxic hemolysin (V. mimicus hemolysin) as a virulence determinant. Vibrio mimicus hemolysin is secreted as an 80 kDa precursor, which is later converted to the 66 kDa mature toxin through removal of an N-terminal propeptide via cleavage of the Arg151-Ser152 bond. In this article, we investigate the role of the endogenous metalloprotease (V. mimicus protease) in the maturation of V. mimicus hemolysin. In vitro experiments using purified proteins showed that, although it activated the precursor at the early stage via cleavage of the Asn157-Val158 bond, V. mimicus protease finally converted the activated and physiologically maturated toxin to a 51 kDa protein through removal of the C-terminal polypeptide. This 51 kDa derivative was unable to lyse erythrocytes because of its inability to bind to the erythrocyte membrane. Vibrio mimicus protease-negative strains were found to produce high levels of V. mimicus hemolysin at the logarithmic phase of bacterial growth and maintained high hemolytic activity even at the stationary phase. These findings indicate that, although it is not directly related to toxin maturation in vivo, V. mimicus protease can modulate the activity of V. mimicus hemolysin and/or its precursor through limited proteolysis.

    DOI: 10.1111/j.1742-4658.2008.06827.x

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担当授業科目

  • コミュニケーション入門 (2020年度) 第4学期  - 火7,火8

  • 微生物学 (2020年度) 3・4学期  - 金3,金4

  • 微生物学 (2020年度) 3・4学期  - 金3,金4

  • 微生物学 (2020年度) 3・4学期  - 金3,金4

  • 薬学基本実習 (2020年度) 特別  - その他

  • 薬学基本実習 (2020年度) 特別  - その他

  • 衛生薬学実習 (2020年度) 特別  - その他

  • 衛生薬学実習 (2020年度) 特別  - その他

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