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Antifungal activity of Lactoferricins and their derivatives

Research Project

Project/Area Number 13470416
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 補綴理工系歯学
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

HAMADA Taizo  Graduate School of Biomedical Sciences Professor, 大学院・医歯薬学総合研究科, 教授 (50034244)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Masahiro  Graduate School of Biomedical Sciences Research Associate, 大学院・医歯薬学総合研究科, 助手 (00294570)
MURATA Hiroshi  Graduate School of Biomedical Sciences Research Associate, 大学院・医歯薬学総合研究科, 助手 (40229993)
NIKAWA Hiroki  University Dental Hospital Assistant Professor, 歯学部附属病院, 講師 (10228140)
ABEKURA Hitoshi  Graduate School of Biomedical Sciences Research Associate, 大学院・医歯薬学総合研究科, 助手 (30159454)
熊谷 宏  広島大学, 歯学部・付属病院, 助手 (60284212)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥9,000,000 (Direct Cost: ¥9,000,000)
Keywordscationic peptide / antifungal activity / Lactoferricins / Histatins / Candida albicans / 殺カンジダ作用 / HIV / Candida / Lactoferricin / Histatin / αへリックス / 両親媒性
Research Abstract

Peptide antibiotics are considered a new class of antifungal agents. Of these, an alpha-helical, cationic peptide termed Dhvar 4, a relative, of salivary histatin has been shown to be an antifungal of relatively high potency. Similarly, lactoferricin B (LFB) and a derivative thereof, LFB(17-30), disrupts the fungal cell membrane and acts against C. albicans. As Dhvar 4 and LFB(17-30), exhibit almost identical amino acid sequences at their C-terminal, we hypothesized that laboratory synthesis of peptides with an alpha-helical structure and having similar amphipathic properties could lead to products with candidacidal activity. Hence, three such peptides - JH8194, JH8195 and JH 8944, were synthesized and their antifungal properties compared with recognized antifungals LFB, LFB (17-30), human lactoferricin (LFH), Histatin-5 and Dhvar 4, against two isolates of C. albicans
The antifungal agents were synthesized and their secondary structures evaluated according to a previously described pro … More tocol of Situ et al. (2000). C. albicans strains were oral isolates from a human immunodeficiency virus (HIV)-infected (isolate A2) and a healthy (A6) individual. A standard concentration of yeasts was exposed to a range of dilutions of the agents for a specific duration and the cell death (viability) in terms of the resultant colony forming units (CFU)/mL was quantified.
Dhvar 4, showed the most alpha-helical propensity, and was the least fungicidal while LFB and LFB(17-30) showed the highest antifungal potential, and demonstrated total kill of A6, and A2 at 5μ and 10μM concentrations, respectively whilst LFH killed both isolates at a 10μM concentration. Of the three new synthetic peptides, JH 8194 was the most potent (total kill of A6/A2 strains at 1.25/2.5μM), followed by JH 8195 (total kill of A6/A2 strains at 5/ 10μM while JH 8944 was the least potent as a 25μM concentration was required to kill either strain of Candida. On further analyses of the relationship between pI value of the peptides and their anticandicidal activity, a significant positive correlation was noted. In order to rule out a cytotoxic effect of the new synthetic peptides we compared the fungicidal and hemolytic activities under similar incubation conditions using freshly isolated erythrocytes and all three peptides exhibited no detectable hemolysis upto a concentration of 100μM in contrast to the polyene antifungal amphotericin B that elicited significant initiation of hemolysis at a concentration of 5.0 μM.
Our data suggest that laboratory synthesis of agents with an alpha-helical structure and having amphipathic properties similar to known, natural antifungal agents may be a promising avenue to generate products with improved antifungal activity. Less

Report

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

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Makihira S. et al.: "Growth of Candida species on commercial denture adhesives in vitro"Int J Prosthodont. 14. 48-52 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nikawa H. et al.: "Candida albicans growth on thermal cycled materials for maxillofacial prostheses in vitro"J Oral Rehabil. 28. 755-765 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nikawa H. et al.: "Susceptibility of Candida albicans isolates from the oral cavities of HIV-positive patients to histatin-5"J Prosthet Dent.. 88. 263-267 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nikawa H. et al.: "Bacterial and Candida adhesion to intact and denatured collagen in vitro"Mycoses. 45. 389-392 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura M et al.: "Cell-associated collagenolytic activity by Candida albicans"Mycopathologia.. 153. 125-128 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 浜田泰三, 二川浩樹, 夕田貞之: "デンタルダイアモンド"義歯の洗浄 デンチャープラークフリーの最前線. 1-137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Makihira S, Nikawa H, Satonobu SV, Jin C, Hamada T.: "Growth of Candida species on commercial denture adhesives in vitro"Int J Prosthodont.. 14(1). 48-52 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nikawa H, Jin C, Hamada T, Makihira S, Polyzois G.: "Candida albicans growth on thermal cycled materials for maxillofacial prostheses in vitroJ Oral Rehabil."J Oral Rehabil.. 28(8). 755-765 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nikawa H, Jin C, Makihira S, Hamada T, Samaranayake LP.: "Susceptibility of Candida albicans isolates from the oral cavities of HIV-positive patients to histatin-5"J Prosthet Dent.. 88(3). 263-267 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Makihira S, Nikawa H, Tamagami M, Hamada T, Nislhimura H, Ishida K, Yamashiro H.: "Bacterial and Candida adhesion to intact and denatured collagen in vitro"Mycoses.. 45(9-10). 389-392 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura M, Nikawa H, Yamashiro H, Nishirnura H, Hamada T, Embery G.: "Cell-associated collagenolytic activity by Candida albicans"Mycopathologia.. 153(3). 125-128 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nikawa H, et al.: "Antifungal activity of Histatin-5 against non-albicans Candida species"Oral Microbiol Immunol. 16. 250-252 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 浜田泰三, 二川浩樹: "デンチャープラークとオーラルヘルスケア"補綴誌. 45. 561-581 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nikawa H, et al.: "Susceptibility of Candida albicans isolates from oral cavities of HIV positive patients to histatin-5"J Prosthet Dent. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report

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

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