基本情報
- 所属
- 自治医科大学 医学部感染・免疫学講座 細菌学部門 教授
- 学位
- (BLANK)
- 研究者番号
- 50306932
- ORCID ID
- https://orcid.org/0000-0002-8909-3885
- J-GLOBAL ID
- 200901096624649406
- researchmap会員ID
- 1000264314
- 外部リンク
経歴
9-
2015年4月 - 現在
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2012年2月 - 2015年3月
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2007年4月 - 2012年1月
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2002年4月 - 2007年3月
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1998年4月 - 2002年3月
学歴
2-
- 1994年
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- 1985年
委員歴
8-
2022年1月 - 現在
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2021年7月 - 現在
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2018年5月 - 現在
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2013年 - 現在
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2012年 - 現在
受賞
4論文
104-
Communications biology 7(1) 1129-1129 2024年9月13日In response to the escalating antibiotic resistance in multidrug-resistant pathogens, we propose an innovative phagemid-based capsid system to generate CRISPR-Cas13a-loaded antibacterial capsids (AB-capsids) for targeted therapy against multidrug-resistant Staphylococcus aureus. Our optimized phagemid system maximizes AB-capsid yield and purity, showing a positive correlation with phagemid copy number. Notably, an 8.65-fold increase in copy number results in a 2.54-fold rise in AB-capsid generation. Phagemids carrying terL-terS-rinA-rinB (prophage-encoded packaging site genes) consistently exhibit high packaging efficiency, and the generation of AB-capsids using lysogenized hosts with terL-terS deletion resulted in comparatively lower level of wild-type phage contamination, with minimal compromise on AB-capsid yield. These generated AB-capsids selectively eliminate S. aureus strains carrying the target gene while sparing non-target strains. In conclusion, our phagemid-based capsid system stands as a promising avenue for developing sequence-specific bactericidal agents, offering a streamlined approach to combat antibiotic-resistant pathogens within the constraints of efficient production and targeted efficacy.
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Antibiotics 13(9) 870-870 2024年9月11日Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices.
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Scientific reports 14(1) 16225-16225 2024年7月13日In response to the escalating global threat of antimicrobial resistance, our laboratory has established a phagemid packaging system for the generation of CRISPR-Cas13a-antimicrobial capsids targeting methicillin-resistant Staphylococcus aureus (MRSA). However, a significant challenge arose during the packaging process: the unintentional production of wild-type phages alongside the antimicrobial capsids. To address this issue, the phagemid packaging system was optimized by strategically incorporated silent mutations. This approach effectively minimized contamination risks without compromising packaging efficiency. The study identified the indispensable role of phage packaging genes, particularly terL-terS, in efficient phagemid packaging. Additionally, the elimination of homologous sequences between the phagemid and wild-type phage genome was crucial in preventing wild-type phage contamination. The optimized phagemid-LSAB(mosaic) demonstrated sequence-specific killing, efficiently eliminating MRSA strains carrying target antibiotic-resistant genes. While acknowledging the need for further exploration across bacterial species and in vivo validation, this refined phagemid packaging system offers a valuable advancement in the development of CRISPR-Cas13a-based antimicrobials, shedding light on potential solutions in the ongoing battle against bacterial infections.
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Critical Reviews in Microbiology 1-22 2024年7月 査読有り
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Communications Biology 7(1) 2024年5月6日Abstract Escherichia coli O157 can cause foodborne outbreaks, with infection leading to severe disease such as hemolytic-uremic syndrome. Although phage-based detection methods for E. coli O157 are being explored, research on their specificity with clinical isolates is lacking. Here, we describe an in vitro assembly-based synthesis of vB_Eco4M-7, an O157 antigen-specific phage with a 68-kb genome, and its use as a proof of concept for E. coli O157 detection. Linking the detection tag to the C-terminus of the tail fiber protein, gp27 produces the greatest detection sensitivity of the 20 insertions sites tested. The constructed phage detects all 53 diverse clinical isolates of E. coli O157, clearly distinguishing them from 35 clinical isolates of non-O157 Shiga toxin-producing E. coli. Our efficient phage synthesis methods can be applied to other pathogenic bacteria for a variety of applications, including phage-based detection and phage therapy.
MISC
164-
日本細菌学雑誌 57(1) 189-189 2002年2月
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TRENDS IN MICROBIOLOGY 9(10) 486-493 2001年10月Significant advances have been made in recent years in our understanding of how methicillin resistance is acquired by Staphylococcus aureus. Integration of a staphylococcal cassette chromosome mec(SCCmec) element into the chromosome converts drug-sensitive S. aureus into the notorious hospital pathogen methicilin-resistant S. aureus(MRSA), which is resistant to practically all beta -lactam antibiotics. SCCmec is a novel class of mobile genetic element that is composed of the mec gene complex encoding methicillin resistance and the ccr gene complex that encodes recombinases responsible for its mobility. These elements also carry various resistance genes for non-beta -lactam antibiotics. After acquiring an SCCmec element, MRSA undergoes several mutational events and evolves into the most difficult-to-treat pathogen in hospitals, against which all extant antibiotics including vancomycin are ineffective. Recent epidemiological data imply that MRSA has embarked on another evolutionary path as a community pathogen, as at least one novel SCCmec element seems to have been successful in converting S. aureus strains from the normal human flora into MRSA.
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日本細菌学雑誌 56(1) 281-281 2001年2月
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日本化学療法学会雜誌 = Japanese journal of chemotherapy 47(6) 339-344 1999年6月25日
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The Japanese Journal of Antibiotics 51(12) 735-745 1998年12月コアグラーゼ陰性ブドウ球菌(CNS)のVancomycin(VCM)とTeicoplanin(TEIC)に対する感受性及び培地の影響について検討した.Staphylococcus epidermidisの1980年〜1981年分離菌に対するVCMとTEICのMIC値をNCCLSの基準で測定するとMueller-Hinton agar(MHA)とBrain Heart Infusion agar(BHIA)のどちらの培地を用いた場合でも,両薬剤に対して全て感性であった.また,1994年〜1997年分離菌のVCMに対する感性率はMHAで99.2%,BHIAで68.0%であった.同様に,TEICに対するMHAとBHIAでの感性率はそれぞれ97.5%,77.9%であり,年次的に感性率は低下していた
書籍等出版物
1共同研究・競争的資金等の研究課題
23-
日本学術振興会 科学研究費助成事業 2024年4月 - 2029年3月
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2024年4月 - 2026年3月
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日本医療研究開発機構 (AMED) 医薬品研究開発 2021年 - 2026年
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日本医療研究開発機構 (AMED) AMED-CREST 2021年 - 2026年
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日本学術振興会 科学研究費助成事業 2022年6月 - 2024年3月
産業財産権
3-
特開2000-060597
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特開2001-275696
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特開2004-254502