Biological investigation of antimicrobial peptides for the regulation of fungal infections
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Kochi Medical School|
UETA Eisaku Kochi Medical School, Department of Oral Surgery, Assistant Professor, 医学部附属病院, 講師 (10203431)
OKU Naohisa Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部附属病院, 助手 (20363286)
KAMATANI Takaaki Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部附属病院, 助手 (00315003)
SASABE Eri Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部附属病院, 助手 (40363288)
OSAKI Toki Kochi Medical School, Department of Oral Surgery, Professor, 医学部, 教授 (70031995)
木村 剛 高知医科大学, 医学部附属病院, 助手 (10294836)
山本 哲也 高知医科大学, 医学部, 助教授 (00200824)
|Project Period (FY)
2002 – 2003
Completed(Fiscal Year 2003)
|Budget Amount *help
¥9,700,000 (Direct Cost : ¥9,700,000)
Fiscal Year 2003 : ¥4,400,000 (Direct Cost : ¥4,400,000)
Fiscal Year 2002 : ¥5,300,000 (Direct Cost : ¥5,300,000)
|Keywords||antimicrobial peptide / α-defensin / β-defensin / Peptide 2 / cytochrome P450 / candidiasis / aspergillosis / neutrophils / Peptide2 / チトクロームp450 / カンジタ症|
We examined the antifungal mechanisms of antimicrobial peptides including lactoferrin peptide, Peptide 2, which was made by our laboratoies.
1. Peptide 2 possesses stronger antifungal effect against both C.albicans and A.fumigatus than α-defensin-1 and β-defesin-2.
2. Peptide 2 and Histatin 5 show additive and synergistic effects with amphotericin B and intraconazol, respectively.
3. Intracellular concentration of the antifungal drugs increased when the fungi were treated with a combination with each antifungal drug and Peptide 2, Histatin 5 or α-defensin-1.
4. Each antimicrobial peptide weakly inhibited syntheses of Candida cell wall (chicin, mannan, glucan) and DNA but did not inhibit the cytochrome P450 activity of each fungus. Each antimicrobial peptide increased ATP-efflux from Candida cells with no increase of the membrane permeability.
5. Each antimicrobial peptide, especially Peptide 2, prolonged the survival periods of Candida- and Aspergillus-infected mice cooperating with each antifungal drug.
6.Although both antifungal drugs increased the multidrug-resistance gene (MDR1), Peptide 2 and Histatin 5 did not increase the MDR1 and bothe peptides revealed almost equal anticellular activities against amphotericin B-resistant Candida cells.
7. In the peptide examined, only Peptide 2 enhanced neutrophil killing activity and reactive oxygen species (ROS)-generating activity.
8. Peptide 2, but not other peptides, increased ROS generation and phagocytosis of neutrophils activating the signal pathway of G protein, PI3K, PKC, PAK1 and ERK1/2 and increasing the expression of Rac2/Cdc2,p47^<phox> and p67^<phox>.
These results suggest that Peptide 2 is clinically useful for treatment of fungal infections.
Research Products (10results)