研究職歴 2022- , 信州大学 先鋭領域融合研究群バイオメディカル研究所 助教 (特定雇用) 2022-2022 , Northeastern University Antimicrobial Discovery Center Associate Research Scientist 2015-2022 , Northeastern University Antimicrobial Discovery Center Postdoctoral Research Associate
研究活動業績
研究業績(著書・ 発表論文等)
論文 Phenomenological interpretations of the mechanism for the concentration-dependent positive effect of antibiotic lincomycin on Streptomyces coelicolor A3(2) Applied and Environmental Microbiology 2023(Sep. 21) Author:Keiichiro Mukai; Tomoko Shibayama; Yu Imai; Takeshi Hosaka Abstract:ABSTRACT
The antibiotic lincomycin binds to the 23S ribosomal RNA peptidyl transferase loop region to inhibit protein synthesis. However, lincomycin can also stimulate the growth and secondary metabolism of actinomycetes in a concentration-dependent manner. In Streptomyces coelicolor A3(2), lincomycin stimulates the production of the blue-pigmented antibiotic actinorhodin at concentrations below the minimum inhibitory concentration. To better understand the molecular mechanism underlying these concentration-dependent positive effects, this study investigated how the target molecule, the ribosome, undergoes dynamic changes in the presence of lincomycin and explored the ribosome-related factors involved. Lincomycin, at a concentration that stimulates actinorhodin production of S. coelicolor A3(2), could restore temporarily arrested ribosome function by utilizing ribosome-related proteins and translation factors, presumably under the control of the transcription factor WblC protein that confers intrinsic resistance to multiple translation-inhibiting antibiotics, to eventually produce stable and active ribosomes even during the late growth phase. This qualitatively and quantitatively positive ribosome alteration can be advantageous for producing actinorhodin biosynthetic enzymes. A series of gene expression and biochemical analyses revealed that lincomycin at the concentration that induces ribosomal stabilization in S. coelicolor A3(2) could influence the localization of the 20S proteasome-related proteins, resulting in reduced proteasome activity. These findings suggest that the functional analysis of 20S proteasome represents a potential pivotal challenge for understanding the molecular mechanism of ribosome stabilization induced by lincomycin. Therefore, as lincomycin can dynamically alter its target molecule, the ribosome, we discuss the future issues and prospects for an increased understanding of the concentration-dependent properties of antibiotics.
IMPORTANCE
Antibiotics were originally defined as chemical compounds produced by a microbe that inhibits the growth of other microbes. However, an unexplained effect of this is that a low concentration of antibiotics, such as those below the minimum inhibitory concentration, can positively affect microbial growth and metabolism. The secondary metabolic activation of streptomycetes in the presence of the translation-inhibiting antibiotic lincomycin illustrates the concentration-dependent positive effect of the antibiotic. The significance of this study is that the phenomenological interpretation of the molecular mechanism of the concentration-dependent positive effect of lincomycin in Streptomyces coelicolor A3(2) has provided novel insight into the possible role of antibiotics in making their target molecules stable and active with the assistance of various related factors that benefit their function. Further exploration of this idea would lead to an essential understanding of antibiotics, including why actinomycetes make them and their role in nature.
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The antibiotic darobactin mimics a β-strand to inhibit outer membrane insertase Nature,593(7857):125-129 2021(Apr.) Author:Hundeep Kaur; Roman P. Jakob; Jan K. Marzinek; Robert Green; Yu Imai; Jani Reddy Bolla; Elia Agustoni; Carol V. Robinson; Peter J. Bond; Kim Lewis; Timm Maier; Sebastian Hiller
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A new antibiotic selectively kills Gram-negative pathogens Nature,576(7787):459-464 2019(Dec.) Author:Yu Imai*; Kirsten J. Meyer*; Akira Iinishi; Quentin Favre-Godal; Robert Green; Sylvie Manuse; Mariaelena Caboni; Miho Mori; Samantha Niles; Meghan Ghiglieri; Chandrashekhar Honrao; Xiaoyu Ma; Jason J. Guo; Alexandros Makriyannis; Luis Linares-Otoya; Nils Böhringer; Zerlina G. Wuisan; Hundeep Kaur; Runrun Wu; André Mateus; Athanasios Typas; Mikhail M. Savitski; Josh L. Espinoza; Aubrie O’Rourke; Karen E. Nelson; Sebastian Hiller; Nicholas Noinaj; Till F. Schäberle; Anthony D’Onofrio; Kim Lewis
A possible mechanism for lincomycin induction of secondary metabolism in Streptomyces coelicolor A3(2) Antonie van Leeuwenhoek,111(5):705-716 2018(May) Author:Misaki Ishizuka*; Yu Imai*; Keiichiro Mukai; Kazuma Shimono; Ryoko Hamauzu; Kozo Ochi; Takeshi Hosaka
Lincomycin at subinhibitory concentrations potentiates secondary metabolite production by Streptomyces spp. Applied and Environmental Microbiology,81(11):3869-3879 2015(Jun.) Author:Yu Imai; Seizo Sato; Yukinori Tanaka; Kozo Ochi; Takeshi Hosaka
Development of the ability to produce secondary metabolites in Streptomyces through the acquisition of erythromycin resistance The Journal of Antibiotics,65(6):323-326 2012(Jun.) Author:Yu Imai; Tatsuya Fujiwara; Kozo Ochi; Takeshi Hosaka
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Mycobacterium tuberculosis を選択的に殺す DNA ジャイレース阻害剤の発見 日本農芸化学会 2022 年度大会 2022(Mar.) Presenter:今井 優; Hauk Glenn; Quigley Jeffrey; Liang Libang; Son Sangkeun; Ghiglieri Meghan; Gates Michael; Morrissette Madeleine; Shahsavari Negar; Niles Samantha; Honrao Chandrashekhar; Ma Xiaoyu; Guo Jason; Berger James; Lewis Kim
3’-amino 3’-deoxyguanosine is a natural nucleoside prodrug antibiotic that selectively kills Escherichia coli 2021 Boston Bacterial Meeting 2021(Jun.) Presenter:N. Shahsavari; Y. Imai; L. Liang; S. Son; N. Böhringer; B. Wang; S. Manuse; M. Morrissette; M. Mori, A; D’Onofrio; M. T. Laub; K. Lewis
Biosynthesis of Darobactin, a novel antibiotic that selectively kills Gram-negative pathogens International VAAM Workshop Biology of Microorganisms Producing Natural Products 2019(Sep.) Presenter:N. Böhringer; Z. G. Wuisan; L. Linares-Otoya; Y. Imai; K. J. Meyer; A. Iinishi; Q. Favre-Godal; R. Green; S. Manuse; M. Caboni; M. Mori; S. Niles; M. Ghiglieri; C. Honrao; X. Ma; J. Guo; A. Makriyannis; A. Mateus; A. Typas; M. M. Savitski; J. L. Espinoza; A. O’Rourke; K. E. Nelson; A. D'Onofrio; K. Lewis; T. F. Schäberle
Heterologous expression of the darobactin biosynthetic gene cluster International VAAM Workshop Biology of Microorganisms Producing Natural Products 2019(Sep.) Presenter:Z.G. Wuisan; N. Böhringer; L. Linares-Otoya; Y. Imai; K. J. Meyer; A. Iinishi; Q. Favre-Godal; R. Green; S. Manuse; M. Caboni; M. Mori; S. Niles; M. Ghiglieri; C. Honrao; X. Ma; J. Guo; A. Makriyannis; A. Mateus; A. Typas; M. M. Savitski; J. L. Espinoza; A. O’Rourke; K. E. Nelson; A. D'Onofrio; K. Lewis; T. F. Schäberle
Specific 23S ribosomal RNA mutations conferring erythromycin resistance can enhance the frequency of spontaneous mutations in Streptomyces strains perturbing their secondary metabolism. The 14th International Symposium on the Genetics of Industrial Microorganisms 2019(Sep.) Presenter:K. Hoshino; Y. Imai; R. Hamauzu; K. Ochi; T. Hosaka
ADC56 is a Novel Antimicrobial Acting against Gram-Negative Pathogen. ASM microbe 2019 2019(Jun.) Presenter:Y. Imai; K. J. Meyer; Q. Favre-Godal; A. Iinishi; M. Caboni; S. E. Niles; M. L. Ghiglieri; R. C. Green; C. Honrao; X. Ma; A. Makriyannis; J. J. Guo; L. Linares-Otoya; N. Böhringer; T. F. Schäberle; A. D'Onofrio; K. Lewis
The Fundamental Mechanism Underlying the Lincomycin Induction of Secondary Metabolism in Streptomyces coelicolor A3(2). ASM microbe 2019 2019(Jun.) Presenter:K. Mukai; M. Ishizuka; M. Kobayashi; Y. Imai; T. Hosaka
Darobactin, a novel antibiotic selectively kills Gram-negative pathogens. 2019 Boston Bacterial Meeting 2019(Jun.) Presenter:Y. Imai; K. J. Meyer; A. Iinishi; Q. Favre-Godal; R. Green; S. Manuse; M. Caboni; M. Mori; S. Niles; M. Ghiglieri; C. Honrao; X. Ma; J. Guo; A. Makriyannis; N. Bohringer; L. Linares-Otoya; A. Mateus; A. Typas; M. M. Savitski; J. L. Espinoza; A. O’Rourke; K. E. Nelson; T. F. Sch ̈aberle; A. D’Onofrio; K. Lewis
Hygromycin A, an antimicrobial with selective activity against Borrelia burgdorferi for treatment of Lyme disease. 256th ACS National Meeting & Exposition 2018(Aug.) Presenter:Y. Imai; X. Wu; M. Caboni; Q. Favre-Godal; S. Niles; K. Megan; A. Iinishi; K. Lewis
23S rRNA gene mutations that perturb occurrence of spontaneous mutations can be indirectly involved in the activation of secondary metabolism of streptomycetes ASM microbe 2018 2018(Jun.) Presenter:K. Hoshino; Y. Imai; R. Hamauzu; T. Hosaka
Genetic and Physiological Characterization of the Erythromycin-resistant and Antibiotic-overproducing Mutants of Streptomyces spp. 18th International Symposium on the Biology of Actinomycetes 2017(May) Presenter:K. Hoshino; Y. Imai; R. Hamauzu; K. Ochi; T. Hosaka
Discovery of a novel antibiotic from unculturable bacteria by utilizing in situ cultivation devise. バイオメディカル研究所セミナー第 12 回特別版 2016(Dec.) Presenter:Y. Imai
Genetic and Physiological Characterization of an antibiotic-overproducing erythromycin-resistant mutant of Streptomyces coelicolor A3(2) The 13th International Symposium on the Genetics of Industrial Microorganisms 2016(Oct.) Presenter:K. Hoshino; Y. Imai; R. Hamauzu; K. Ochi; T. Hosaka
Activation of secondary metabolite production in Streptomyces spp. by exposure to subinhibitory concentrations of lincomycin. International Union of Microbiological Societies 2014 Congress 2014(Jul.) Presenter:Y. Imai; S. Sato; Y. Tanaka; K. Ochi; T. Hosaka
A spontaneous erythromycin resistance mutation in Streptomyces lividans elicits an ability to produce antibacterial compounds. International Union of Microbiological Societies 2011 Congress 2011(Sep.) Presenter:Y. Imai; T. Fujiwara; K. Sen; K. Ochi; T. Hosaka
Activation of “silent genes” in Streptomyces sp. 631689 by generating a spontaneous gentamicin-resistant mutation. 15th International symposium on the biology of the Actinomycetes 2009(Aug.) Presenter:T. Hosaka; T. Fujiwara; Y. Imai; K. Sen; K. Ochi