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Potential Antimicrobial Strategy Using Genetically Engineered Homo & Hetero-Dimer of alpha-Lactalbumin and Lysozyme

Research Project

Project/Area Number 13660129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 食品科学・栄養科学
Research InstitutionKagoshima University

Principal Investigator

IBRAHIM Hisham r.  Kagoshima University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (90274836)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsLysozyme / α-Lactalbumin / Antimicrobial / Interaction / Hetero-Dimer / Pichia Expression System / Mammary Epithelial Cells / New Drug Design / 抗菌性 / ホモダイマー / カルシウム結合 / カルシウム
Research Abstract

Mammalian milk is characterized by a complex host defense system that prevents the growth of microbial pathogens that may pervade the infant. However, little is known of the fate of the antimicrobial components and precisely how they interact to protect the recipient. Alpha-lactalbumin (α-LA) is one of the major proteins in milk of all species and has the unusual property of acting to modify the action of galactosyltransferase to a lactose synthase. On the other hand, lysozyme (LZ), a homologous protein to α-LA, is a ubiquitous antimicrobial in a variety of tissues and secretions. These two proteins uniquely co-exist in mammalian milk but the significance of their distinct presence in milk is completely unknown. In this study, LZ and α-LA were investigated to elucidate the nature of their interaction and antibacterial synergy. A complex of LZ and α-LA exhibited greatly enhanced antibacterial activity against the Gram-positive and -negative bacteria. Under physiological pH, α-LA associa … More ted with LZ, whereas the complex existed mainly as LZ-αLA heterodimer with LZ homodimer. The results provided the first demonstration of association of α-LA with LZ leading to the formation of a distinct complex with significantly enhanced bactericidal activity. Our results strongly suggest the important role of LZ and α-LA in the host defense system of the newborn against gastric microbial infections. Furthermore, a parallel genetic study was initiated with the objectives of cloning the cDNAs of human LZ (hLZ) and human LA (hLA) from human mammary epithelial cells, establish high-level expression system in Pichia under the native signal peptides of the two human proteins, and to design a stable in-frame fusion constructs between hLZ and hLA., Human LZ, α-LA, and their LZ-α-LA fusion construct were successfully produced in Pichia methanolica with expression level exceeding 20 mg/L and thus offer a great opportunity for the design of potential antimicrobial drug in the treatment of infectious diseases. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] H.R.IBRAHIM, T.Matsuzaki, T.Aoki: "Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function."FEBS Letters. 506. 27-32 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, U.Thomas, A.Pellegrini: "A helix-loop-helix peptide at the upper lip of the active site cleft of Lysozyme confers potent antimicrobial activity with membrane permeabilization action."Journal of Biological Chemistry. 276(47). 43767-43774 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, T Aoki, A.Pellegini: "Strategies for New Antimicrobial Proteins and Peptides : Lysozyme and Aprotinin as Model Molecules."Current Pharmaceutical Design. 8(9). 671-693 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, T Aoki: "New Promises of Lysozyme as Immune Modulator and Antimicrobial Agent for Nutraceuticals."Foods & Food Ingredients Journal. 208(5). 361-374 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, N.Taniyama, T.Aoki: "Distinct dimerization between α-lactalbumin and Lysozyme exhibiting novel antimicrobial activity against gram-positive and gram-negative bacteria"Letters in Drug Design & Discovery. 1(2). 101-109 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, T.Matsuzaki, T.Aoki: "Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function"FEBS Letters. 506. 27-32 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, U.Thomas, A.Pellegrini: "A helix-loop-helix peptide at the upper lip of the active site cleft of lysozyme confers potent antimicrobial activity with membrane permeabilization action"Journal of Biological Chemistry. 276(47). 43767-43774 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, T.Aoki, A.Pellegrini: "Strategies for New Antimicrobial Proteins and Peptides : Lysozyme and Aprotinin as Model Molecules"Current Pharmaceutical Design. 8(9). 671-693 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, T.Aoki: "New Promises of Lysozyme as Immune Modulator and Antimicrobial Agent for Nutraceuticals"Foods & Food Ingredients Journal. 208(5). 361-374 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, N.Taniyama, T.Aoki: "Distinct dimerization between α-lactalbumin and lysozyme exhibiting novel antimicrobial activity against gram-positive and gram-negative bacteria"Letters in Drug Design & Discovery. 1(2). 101-109 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.R.IBRAHIM, T.Matsuzaki, T.Aoki: "Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function"FEBS Letters. 506. 27-32 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.R.IBRAHIM, U.Thomas, A.Pellegrini: "A helix-loop-helix peptide at the upper lip of the active site cleft of lysozyme confers potent antimicrobial activity with membrane permeabilization action"Journal of Biological Chemistry. 276(47). 43767-43774 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.R.IBRAHIM, T.Aoki, A.Pellegrini: "Strategies for New Antimicrobial Proteins and Peptides : Lysozyme and Aprotinin as Model Molecules"Current Pharmaceutical Design. 8(9). 671-693 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] R.IBRAHIM, T.Aoki: "New Promises of Lysozyme as Immune Modulator and Antimicrobial Agent for Nutraceuticals"Foods & Food Ingredients Journal. 208(5). 361-374 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.R.IBRAHIM, N.Taniyama, T.Aoki: "Distinct dimerization between a-lactalbumin and lysozyme exhibiting novel antimicrobial activity against gram-positive and gram-negative bacteria"Letters in Drug Design & Discovery. 1(2). 35-44 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.R.IBRAHIM, T.Matsuzaki, T.Aoki: "Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function"FEBS Letters. 506. 27-32 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.R.IBRAHIM, U.Thomas, A.Pellegrini: "A helix-loop-helix peptide at the upper lip of the active site cleft of lysozyme confers potent antimicrobial activity with membrane permeabilization action"Journal of Biological Chemistry. 276(47). 43767-43774 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.R.IBRAHIM, T.Aoki, A.Pellegrini: "Strategies for New Antimicrobial Proteins and Peptides : Lysozyme and Aprotinin as Model Molecules"Current Pharmaceutical Design. 8(9). 671-693 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.R.IBRAHIM, T.Aoki: "New Promises of Lysozyme as Immune Modulator and Antimicrobial Agent for Nutraceuticals"Journal of Foods & Food Ingredients. (In Press).

    • Related Report
      2002 Annual Research Report
  • [Publications] H.R.IBRAHIM, T.Matsuzaki, T.Aoki: "Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function"FEBS Letters. 506. 27-32 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.R.IBRAHIM, U.Thomas, A.Pellegrini: "A helix-loop-helix peptide at the upper lip of the active site cleff of lysozyme confers potent antimicrobial activity with membrane permeabilization action"The Journal of Biological chemistry. 276(47). 43767-43774 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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